1 Department of Molecular
Medicine, The proprotein-processing endoprotease furin is
localized in the gastric epithelial cells of the pit region in the rat
gastric gland. The gastric pit is composed of several cell types,
including gastric surface mucosal (GSM) cells and parietal cells. Furin converts many growth- or differentiation-related proproteins to their
active forms. We examined identification of furin-positive cells by
immunostaining of rat gastric mucosa and regulators of the furin
expression by measuring the furin promoter activity by luciferase
assay. Furin-positive cells were stained for
H+-K+-ATPase,
indicating that they are parietal cells. Furin-positive parietal cells
were not stained for transforming growth factor-
transforming growth factor- THE GASTRIC PIT REGION is composed of several cell
types, including gastric surface mucous (GSM) cells (also called pit
cells) and parietal cells (17-19). These cells arise from
granule-free precursor cells in the proliferative zone at the isthmus
of the gastric gland. From the proliferative zone, GSM cells move
upward to the luminal surface of gastric glands, with a lifetime of
~3 days in mice (19). Parietal cells move both upward and downward; the ratio of upward-moving and downward-moving cells was reported as
half and half (17). In the pit, parietal cells distribute from the
middle of the pit to near the proliferative zone and have a lifetime of
54 days in mice. The parietal cells develop mostly from the parietal
cell precursors to preparietal cells, but a fraction of parietal cells
develop from prepit cell precursors and preneck cell precursors (17).
Thus prepit cell precursors have the potential to develop into either
prepit or preparietal cells.
GSM cells develop into their well-differentiated form in three stages:
a prepit cell stage, a mature pit cell stage, and a final top-pit cell
stage. Cell-stage differentiation is well characterized by the
appearance of mucus-containing secretory granules that begin to appear
at the prepit cell stage and increase in great number to the mature pit
cell stage (15, 19). In addition to these mucus-containing granules,
the cells express transforming growth factor- Recently, we found that the proprotein-processing endoprotease furin is
distributed around the upper one-fourth of the gastric gland of the
adult rat (21). This furin-positive cell zone is a little higher than
the proliferative zone. Furin cleaves the carboxy-terminal end of
We previously investigated the expression of furin and TGF- In the rat gastric pit, furin-positive cells are localized a little
higher than the proliferative zone (21). Because furin-positive GSM06
cells become TGF- Morphological studies.
Male Wistar rats (150-200 g) were purchased from Imai Experimental
Animal Farm (Saitama, Japan). The rats were maintained under controlled
light (7:00 AM to 7:00 PM) with food and water provided ad libitum.
When their stomachs were used for morphological studies, they were
fasted for 24 h and then killed. Stomachs were minced and fixed in 4%
paraformaldehyde in 0.1 M phosphate buffer, pH 7.4, at 4°C for 24 h. Small pieces of minced tissue underwent saccharose replacement and
were embedded in OCT compound for frozen sectioning by a microtome.
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
(TGF-
) but were
surrounded by TGF-
-positive GSM cells. In contrast, parietal cells
below the proliferative zone were positive for TGF-
but not for
furin. Furin-positive parietal cells expressed a high level of
epidermal growth factor receptor (EGFR). TGF-
stimulated the furin
promoter activity highly in a mouse GSM cell line GSM06. Thus we
suggest that the parietal cells of the pit region have furin-mediated
functions that can be stimulated by EGFR signaling.
; gastric surface mucous cells; gastric pit
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
(TGF-
) with
differentiation (13, 29). TGF-
shares a common receptor with
epidermal growth factor (EGF), EGFR, and with heparin-binding EGF-like
growth factor (HB-EGF) (26). EGFR is expressed in parietal cells and
GSM cells (30, 34). Thus TGF-
and EGFR are abundantly expressed in
the pit region. Although TGF-
is known to induce cell proliferation
in primary-cultured rat GSM cells (5), its receptor distribution in
terminally differentiated GSM and parietal cells may suggest that
TGF-
exerts nonproliferative functions in the gastric gland.
Arg
4-X-(Lys/Arg)
2-Arg
1,
which is found in many growth-related precursor proteins (14, 28).
These precursor proteins include adhesion molecules such as a
procadherin family and integrin subunits
3 and
6, matrix metalloproteinases
(MMP) such as stromelysin-3 and membrane-type MMP, several growth
factor precursors including platelet-derived growth factor, human
HB-EGF (27), transforming growth factor-
, and parathyroid
hormone-related protein, and, in some growth factor proreceptors such
as insulin receptor, insulin-like growth factor-1 receptor and
hepatocyte growth factor receptor (oncoprotein MET). Because many of
these precursor proteins with furin-cleavable sites are expressed in
the gastric mucosa, furin may be involved in the growth and
differentiation of mucosal cells.
using a
GSM cell line, GSM06 (21). This cell line is derived from the GSM cells
of a transgenic mouse that was transformed with the
temperature-sensitive SV40 T antigen (35). At high temperature
(39°C), at which the SV40 T antigen is inactivated, the GSM06 cells
exhibit growth arrest and exhibit differentiated features, such as the
production of periodic acid-Schiff-positive materials, secretory
granules, and expression of TGF-
. In contrast, when the cells are
exposed to 33°C, they start growing by acquiring a characteristic
of T antigen-transformed cells and express a high level of furin and a
diminished low level of TGF-
.
positive when placed in a differentiation-inducing condition (39°C and/or confluent state), we presumed that
furin-positive cells may become TGF-
-positive cells during the pit
cell lineage differentiation in the normal gastric mucosa. In this
paper, we investigated the topological relation of furin-positive and
TGF-
-positive cells in the rat gastric glands, the cellular
characteristics of the furin-positive cells, and the effect of TGF-
as well as other growth factors on the expression of furin.
MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
from Calbiochem-Novabiochem (San Diego, CA), and sheep antibody to EGFR
from Upstate Biotechnology (Lake Placid, NY). F-actin was stained with
FITC-labeled phalloidin (Molecular Probes, San Diego, CA).
Stimulation of acid secretion. Physiological saline (100 µl) containing 100 µM histamine and carbachol (300 mg/kg body wt) was injected subcutaneously into rats. After 30 min, the stomachs were removed and subjected to the above-described fixation and immunostaining process.
Plasmid construction.
A human furin 5'-upstream sequence was cloned from the human
genomic library using oligonucleotide probes based on the previously reported sequence (2). The furin gene possesses the three alternative 5'-noncoding exons. Of the three, only exon 1 has a TATA box and is activated by transcription factor CAAT enhancer binding protein- (C/EBP-
). The other two, exons 1A and 1B, have
characteristics of promoters for housekeeping genes. Thus we used the
TATA box containing furin promoter in this study. Four
5'-upstream DNA fragments,
3633/+55
(Pst
I-Pst I),
1092/+55
(Bgl
II-Pst I),
612/+55
(Xba
I-Pst I), and
56/+55
(BamH
I-Pst I), were placed before a firefly
luciferase gene supplied with the Dual-Luciferase reporter assay system
(Promega, Madison, WI).
Cell culture and luciferase assay.
As a culture model for the surface mucosal cells, we used a GSM06 cell
line (35). The cells were cultured on a collagen type I-coated plastic
plate (Iwaki, Tokyo, Japan) in DMEM-Ham's F-12 medium (Sigma, St.
Louis, MO) supplemented with 10% fetal bovine serum (GIBCO, Grand
Island, NY) and 1% ITES (100% ITES: 2 mg/l insulin, 2 mg/l
transferrin, 0.122 mg/l ethanolamine, and 9.14 µg/l sodium selenite)
in a humidified 5% CO2 atmosphere
at 33°C unless otherwise indicated. Luciferase activity was assayed by transient gene expression in GSM06 cells. GSM06 cells were seeded
initially at 5 × 105
cells/10-cm plate and cultured for 2 days. Transfection was carried out
with each of the five luciferase gene constructs, including a
promoterless gene, together with the sea pansy luciferase gene placed
under several ubiquitous promoters as an internal standard, using a
DOSPER liposomal transfection reagent (Boehringer Manheim, Mannheim,
Germany). Twenty-four hours after the transfection, the medium was
changed to a new one and the culture was continued for another 6 h. The
cells were then harvested to prepare cell lysates using the cell lysis
buffer supplied with the Dual-Luciferase reporter assay system
(Promega). Stimulants were obtained from the following suppliers:
phorbol 12-myristate 13-acetate (PMA) from Sigma Chemical, TGF- and
EGF from Collaborative Biomedical Products (Bedford, MA), and
platelet-derived growth factor-BB from Genzyme (Cambridge, MA).
Mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor PD-098059
was obtained from Research Biochemicals International (Natick, MA).
Protein kinase C (PKC) inhibitor H-7 was obtained from Seikagaku
(Tokyo, Japan). Each of these stimulants was added at the change of
medium, 24 h after transfection; the cells were then incubated for
another 6 h before harvest. The reaction was initiated by the addition
of 100 µl of the luciferin solution to 50 µl of cell lysate (~100
µg protein), and light emission was measured for 10 s using a
luminometer. Luciferase activity was measured as arbitrary light units
per 10 s per 100 µg protein. Protein concentrations were determined by the Bradford method. Luciferase activity is expressed as
multiplicity (-fold) against the value obtained by the promoterless
luciferase gene or as a percentage against the control value obtained
without stimulants.
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RESULTS |
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Distribution of furin-positive cells in the rat gastric mucosa.
We examined the distribution of PCNA-positive cells, furin-positive
cells, and TGF--positive cells in the rat gastric mucosa (Fig.
1,
A-F).
Black staining of PCNA was localized to nuclei in the gastric mucosal
cells, which have a relatively small cell size (Fig. 1,
D and
E). Most PCNA-positive cells were
distributed around one-third down the gastric gland relative to the
luminal surface, although there were several positive cells in the
glandular region (Fig. 1, A and
B). Overlapping with a higher level
of the PCNA-positive cell layer, the furin-positive cells were
distributed upward in a scatter pattern around one-fourth down the
gastric gland relative to the luminal surface (brown cells in Fig.
1A and black cells in Fig.
1C). Furin-positive cells looked
larger than PCNA-positive cells (Fig. 1,
D and
F). In Fig.
1E, large TGF-
-negative cells
appeared to be furin-positive when compared with furin-positive cells
in Fig. 1, D and
F. The furin-positive cells decreased
in number toward the luminal surface, but staining became heavier and
occupied the entire cytoplasm (Fig. 1,
D and F). Furin-positive staining was also
observed in the lower glandular cells, whose distribution may be due to
chief cells, as determined by their location (Fig. 1,
A and
C). TGF-
-positive cells were distributed further upward in the pit region, but the luminal top-pit
region was negative for TGF-
(Fig. 1,
B and
C). TGF-
staining, apparently in
the parietal cells of the glandular region, was distinctly weaker than
that of GSM cells in the pit (Fig. 1,
B and
C). Furin-positive but
TGF-
-negative cells were surrounded by TGF-
-positive GSM cells
(Fig. 1, E and
F). Thus furin-positive cells were
scattered between the PCNA-positive and TGF-
-positive cell layers in
the pit region.
|
Immunohistochemical characterization of furin-positive cells.
Because furin-positive cells looked larger in size and because parietal
cells were distributed in the pit region as well as the glandular
region, we suspected that the furin-positive cells in the gastric pit
might be parietal cells. To examine this possibility, we performed
double immunostaining of furin and
H+-K+-ATPase
because
H+-K+-ATPase
is specifically localized to the tubulovesicles of the resting parietal
cells. The
H+-K+-ATPase-positive
parietal cells distributed from the pit region to the glandular region
of the gastric gland (Fig.
2A). As
expected, furin-positive cells were also positive for
H+-K+-ATPase,
although
H+-K+-ATPase-positive
cells were not always positive for furin in the pit region (Fig. 2).
The population ratio of furin-positive parietal cells to the total
parietal cells located up from the middle of the growth zone was
30.1 ± 2.8% (n = 8).
The staining of
H+-K+-ATPase
in the pit-region parietal cells indicated a complex
tubulovesicle-canaliculus system composed of many small curly
formations (Fig. 2D). Furin staining
distributed along with
H+-K+-ATPase
staining in these cells (Fig. 2,
D-F).
|
|
|
EGF receptor localization in the pit region.
Because furin-positive parietal cells were surrounded by
TGF--positive GSM cells in the pit region (Fig. 1,
C and
F) and because TGF-
is situated
extracellularly on its membrane-bound precursor (24), we examined the
distribution of its receptor EGFR in the gastric pit. EGFR was stained
over the whole gastric mucosa, especially in the top-pit and glandular
regions (Fig. 5B), as
reported previously (30, 34). In the pit, parietal cells were stained
strongly for EGFR (Fig. 5, D and
E). The
H+-K+-ATPase-containing
tubulovesicle-canaliculus system looked surrounded by EGFR-positive
stainings (Fig. 5F). GSM cells were
apparently stained for EGFR in a punctate manner but much weaker than
the staining of parietal cells (Fig. 5,
D and
E). In contrast, the parietal cells
of the glandular region were stained for EGFR less strongly than the
pit-region parietal cells (Fig. 5, G
and H). Instead, we found strong
EGFR-positive cells distributed next to parietal cells (Fig.
5C and arrows in Fig. 5,
G-I).
By their distribution pattern, these EGFR-positive cells appeared to be chief cells. In general, EGFR-positive parietal cells are surrounded by
TGF-
-positive GSM cells in the gastric pit, whereas TGF-
-positive parietal cells were neighbored by strongly EGFR-positive cells in the
glandular region.
|
Effect of TGF- and other stimulants on the
expression of furin.
GSM cells turn over with a lifetime of ~3 days, whereas parietal
cells possess a lifetime of more than 50 days (17, 19). Thus, during
the movement of TGF-
-positive GSM cells upward among EGFR-positive
and furin-positive parietal cells in the gastric pit, the EGFR-positive
parietal cells may receive juxtacrine signals from TGF-
-positive GSM
cells by cell-to-cell interaction. To examine this possibility, we
measured furin expression by TGF-
and other stimulants with a furin
promoter plus luciferase reporter gene. Although the parietal cell is
the best choice as a target to investigate furin promoter activity, it
is hard to isolate and introduce DNA into parietal cells. To circumvent
this difficulty, we used a GSM06 cell line that expresses EGFR (data
not shown).
|
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DISCUSSION |
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The present study demonstrates that furin-positive cells localized in
the pit region were identified as parietal cells by the presence of
H+-K+-ATPase.
The furin-positive parietal cells were not stained for TGF-, in
contrast to the parietal cells in the glandular region. Instead, the
furin-positive parietal cells were surrounded by TGF-
-positive GSM
cells, suggesting signaling from TGF-
-positive GSM cells to
EGFR-positive parietal cells in the pit region. We further demonstrated
that furin expression was upregulated by TGF-
using a GSM
cell-derived cell line, GSM06.
Most parietal cells are derived from the granule-free precursor cells
localized in the isthmus, from where GSM cells are also derived (17).
By morphological appearance, parietal cells are apparently similar in
any region, except those in the lower base. Karam et al. (20) reported
functional heterogeneity of parietal cells along the pit-gland axis by
showing very little morphological change in response to acid
secretagogues, in contrast to the typical morphological transformation
of parietal cells in other regions. In this study, we demonstrate that
parietal cells displayed different features over and below the
proliferative zone in the isthmus. The distinct features of parietal
cells in the pit region were their larger size, the complex form of the
tubulovesicle-canaliculus system, expression of furin, and
absence of TGF-, compared with those in the neck to base regions.
Parietal cells that possess EGFR stay in the pit for 50-60 days,
whereas TGF--positive GSM cells migrate upward from the proliferative zone to the top-pit region by 3 days (17, 19). Thus, when
GSM cells pass by parietal cells, both cell types may exchange
important signals for cell differentiation by cell-to-cell interaction.
Using canine oxyntic mucosal cell culture, Chen et al. (4) demonstrated
that GSM cells that are in contact with parietal cells display DNA
synthesis and suggested that TGF-
from parietal cells stimulates the
growth of GSM cells in vivo. However, in the rat gastric pit, parietal
cells do not express TGF-
but express EGFR extensively, whereas GSM
cells express TGF-
strongly and EGFR weakly. Thus we think that the
TGF-
signal moves from GSM cells to parietal cells in the pit. In
the glandular region, parietal cells express TGF-
to a moderate
extent, so TGF-
-positive parietal cells can stimulate EGFR-positive
GSM cells in the mixed culture of gastric mucosal cells (4).
The absence of PCNA-positive staining suggests that parietal cells and
GSM cells were not proliferating and thus that TGF--to-EGFR signaling in the pit may not be growth promoting but rather cell differentiating. Recently, Miyoshi et al. (25) demonstrated that the
membrane-bound form of HB-EGF suppresses cell growth and promotes
survival of rat hepatoma-derived AH66tc cells; in contrast, a soluble
form of HB-EGF cleaved from the membrane-bound form increases cell
growth of AH66tc cells. Takemura et al. (36) also showed a distinct
feature of soluble and membrane-bound forms of HB-EGF using a renal
epithelial cell line, NRK-52E. HB-EGF as well as TGF-
precursors are
thought to be processed to their active forms by MMP-like endoproteases
(12). Thus the effect of membrane-bound TGF-
on GSM cell membranes
may maintain the survival of EGFR-expressing parietal cells, resulting
in a long lifespan for parietal cells.
TGF- is known to suppress acid secretion acutely from parietal cells
(33, 38), but its chronic effect increases acid secretion in isolated
parietal cells (6). We suspected that parietal cells in the pit display
similar acid secretion function to those in the glandular region. The
parietal cells displayed horseshoe-shaped morphological transformation
when stimulated with acid secretagogues. Thus we think that acid
secretion is possible in the pit-region parietal cells
under strong TGF-
signaling. Interestingly, Kaise et al. (16)
demonstrated that EGF increases the promoter activity of
H+-K+-ATPase
-subunit gene in isolated canine parietal cells (16). We also
measured a furin promoter activity using luciferase as a reporter gene
and found that TGF-
and the phorbol ester PMA stimulate furin gene
expression in GSM06 cells. Although caution is required when
extrapolating this result to in vivo gastric mucosa, we presume that
TGF-
signaling from GSM cell membranes stimulates furin gene
expression as well as
H+-K+-ATPase
-subunit gene expression in parietal cells (16).
TGF- is released from its membrane-bound precursor by
metalloproteinases (1), which are stimulated by PMA through a
PKC-mediated pathway (10, 31). It is important to identify the natural stimulants leading to metalloproteinase activation through this PKC-mediated pathway in the gastric mucosa. Although furin does not
activate TGF-
processing and also TGF-
-activating
metalloproteinase processing, furin expressed by EGFR signaling may
activate other growth-related proteins to their active forms that
facilitate cell growth or differentiation in an autocrine and/or
paracrine fashion. Several candidate proproteins can be nominated,
including procadherin, integrin subunits
3 and
6, membrane-type MMP MT1-MMP, and parathyroid hormone-related protein, as described in the
introduction (14, 28). The pit-region parietal cells may produce
furin-activated proteins and/or secrete a truncated form of furin
itself that activates proproteins in extracellular space (37). After
activation by furin, these proteins may exert their effect on GSM
cells. At present, these substrate proteins remain to be identified.
Parietal cells play a pivotal role in maintaining gastric mucosal cell
structure because parietal cell-deleted mouse mucosa exhibit atrophic
gastritis-like appearance (3, 22). In this study, we found that
parietal cells are distinct in the expression of furin and TGF- over
and below the proliferative zone. We suggest that pit-region parietal
cells play an essential role in gastric pit structure formation by
producing furin-mediated growth and differentiation factors in contact
with TGF-
-positive GSM cells.
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ACKNOWLEDGEMENTS |
---|
We thank Dr. Norifumi Sugiyama, Molecular Research Laboratory, Daiichi Pharmaceutical, Tokyo 134, for providing a GSM06 cell line; Dr. Kentaro Sugano, Health Care Center, University of Tokyo, and Dr. Kazuhisa Nakayama, Gene Experiment Center, Tsukuba University, for helpful discussions; and Reiko Uchida for secretarial assistance.
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FOOTNOTES |
---|
This work is supported by grants-in-aid from the Ministry of Education, Science, Sports, and Culture.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: T. Takeuchi, Dept. of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma Univ., Showa-machi, Maebashi 371-8512, Japan (E-mail: tstake{at}news.sb.gunma-u.ac.jp).
Received 11 November 1998; accepted in final form 11 April 1999.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Arribas, J.,
F. Lopez-Casillas,
and
J. Massague.
Role of the juxtamembrane domains of the transforming growth factor- precursor and the
-amyloid precursor protein in regulated ectodomain shedding.
J. Biol. Chem.
272:
17160-17165,
1997
2.
Ayoubi, T. Y.,
J. W. M. Creemers,
A. J. M. Roebroek,
and
W. J. M. Van de Ven.
Expression of the dibasic proprotein processing enzyme furin is directed by multiple promoters.
J. Biol. Chem.
269:
9298-9303,
1994
3.
Canfield, V.,
A. B. West,
J. R. Goldenring,
and
R. Levenson.
Genetic ablation of parietal cells in transgenic mice: a new model for analyzing cell lineage relationships in the gastric mucosa.
Proc. Natl. Acad. Sci. USA
93:
2431-2435,
1996
4.
Chen, M. C.,
A. T Lee,
W. F. Karnes,
D. Avedian,
M. Martin,
J. M. Sorvillo,
and
A. H. Soll.
Paracrine control of gastric epithelial cell growth in culture by transforming growth factor-.
Am. J. Physiol.
264 (Gastrointest. Liver Physiol. 27):
G390-G396,
1993
5.
Chen, M. C.,
A. T. Lee,
and
A. H. Soll.
Mitogenic response of canine fundic epithelial cells in short-term culture to transforming growth factor and insulin-like growth factor I.
J. Clin. Invest.
87:
1716-1723,
1991[Medline].
6.
Chew, C. S.,
K. Nakamura,
and
A. C. Petropoulos.
Multiple actions of epidermal growth factor and TGF- on rabbit gastric parietal cell function.
Am. J. Physiol.
267 (Gastrointest. Liver Physiol. 30):
G818-G826,
1994
7.
Dransfield, D. T.,
A. J. Bradford,
J. Smith,
M. Martin,
C. Roy,
P. H. Mangeat,
and
J. R. Goldenring.
Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.
EMBO J.
16:
35-43,
1997
8.
Dudley, D. T.,
L. Pang,
S. J. Decker,
A. J. Bridges,
and
A. R. Saltiel.
A synthetic inhibitor of the mitogen-acticated protein kinase cascade.
Proc. Natl. Acad. Sci. USA
92:
7686-7689,
1995[Abstract].
9.
El-Shemerly, M. Y. M.,
D. Besser,
M. Nagasawa,
and
Y. Nagamine.
12-O-Tetradecanoylphorbol-13-acetate activates the ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of SOS involving serine phosphorylation of shc in NIH3T3 cells.
J. Biol. Chem.
272:
30599-30602,
1997
10.
Harano, T.,
and
K. Mizuno.
Phorbol ester-induced activation of a membrane-bound candidate pro-transforming growth factor- processing enzyme.
J. Biol. Chem.
269:
20305-20311,
1994
11.
Hidaka, H.,
and
M. Hagiwara.
Pharmacology of the isoquinoline sulphonamide protein kinase C inhibitors.
Trends Pharmacol. Sci.
8:
162-164,
1987.
12.
Hooper, N. M.,
E. H. Karran,
and
A. J. Turner.
Membrane protein secretases.
Biochem. J.
321:
265-279,
1997[Medline].
13.
Hormi, K.,
J.-P. Onolfo,
L. Gres,
V. Lebraud,
and
T. Lehy.
Developmental expression of transfoming growth factor- in the upper digestive tract and pancreas of the rat.
Regul. Pept.
55:
67-77,
1995[Medline].
14.
Hosaka, M.,
M. Nagahama,
W-S. Kim,
T. Watanabe,
K. Hatsuzawa,
J. Ikemizu,
K. Murakami,
and
K. Nakayama.
Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway.
J. Biol. Chem.
266:
12127-12130,
1991
15.
Ichikawa, T.,
K. Ishihara,
T. Kusakabe,
M. Kurihara,
T. Kawakami,
T. Takenaka,
K. Saigenji,
and
K. Hotta.
Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO.
Am. J. Physiol.
274 (Gastrointest. Liver Physiol. 37):
G138-G146,
1998
16.
Kaise, M.,
A. Muraoka,
J. Yamada,
and
T. Yamada.
Epidermal growth factor induces H+,K+-ATPase a-subunit gene expression through an element homologous to the 3' half-site of the c-fos serum response element.
J. Biol. Chem.
270:
18637-18642,
1995
17.
Karam, S. M.
Dynamics of epithelial cells in the corpus of the mouse stomach. IV. Bidirectional migration of parietal cells ending in their gradual degeneration and loss.
Anat. Rec.
236:
314-332,
1993[Medline].
18.
Karam, S. M.,
and
C. P. Leblond.
Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell.
Anat. Rec.
236:
259-279,
1993[Medline].
19.
Karam, S. M.,
and
C. P. Leblond.
Dynamics of epithelial cells in the corpus of the mouse stomach. II. Outward migration of pit cells.
Anat. Rec.
236:
280-296,
1993[Medline].
20.
Karam, S. M.,
X. Yao,
and
J. G. Forte.
Functional heterogeneity of parietal cells along the pit-gland axis.
Am. J. Physiol.
272 (Gastrointest. Liver Physiol. 35):
G161-G171,
1997
21.
Konda, Y.,
H. Yokota,
T. Kayo,
T. Horiuchi,
N. Sugiyama,
S. Tanaka,
K. Takata,
and
T. Takeuchi.
Proprotein-processing endoprotease furin controls the growth and differentiation of gastric surface mucous cells.
J. Clin. Invest.
99:
1842-1851,
1997
22.
Li, Q.,
S. M. Karam,
and
J. I. Gordon.
Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice.
J. Biol. Chem.
271:
3671-3676,
1996
23.
Marshall, C. J.
Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
Cell
80:
179-185,
1995[Medline].
24.
Massague, J.,
and
A. Pandiella.
Membrane-anchored growth factors.
Annu. Rev. Biochem.
62:
515-541,
1993[Medline].
25.
Miyoshi, E.,
S. Higashiyama,
T. Nakagawa,
N. Hayashi,
and
N. Taniguchi.
Membrane-anchored heparin-binding epidermal growth factor-like growth factor acts as a tumor survival factor in a hepatoma cell line.
J. Biol. Chem.
272:
14349-14355,
1997
26.
Murayama, Y.,
J-I. Miyagawa,
S. Higashiyama,
S. Kondo,
M. Yabu,
K. Isozaki,
Y. Kayanoki,
S. Kanayama,
Y. Shinomura,
N. Taniguchi,
and
Y. Matsuzawa.
Localization of heparin-binding epidermal growth factor-like growth factor in human gastric mucosa.
Gastroenterology
109:
1051-1059,
1995[Medline].
27.
Nakagawa, T.,
S. Higashiyama,
T. Mitamura,
E. Mekada,
and
N. Taniguchi.
Amino-terminal processing of cell surface heparin-binding epidermal growth factor-like growth factor up-regulates its juxtacrine but not its paracrine growth factor activity.
J. Biol. Chem.
271:
30858-30863,
1996
28.
Nakayama, K.
Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins.
Biochem. J.
327:
625-635,
1997[Medline].
29.
Nasim, M. M.,
D. M. Thomas,
M. R. Alison,
and
M. I. Filipe.
Transforming growth factor expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma
an immunohistochemical study.
Histopathology
20:
339-343,
1992[Medline].
30.
Orsini, B.,
A. Calabro,
S. Milani,
C. Grappone,
H. Herbst,
and
C. Surrenti.
Localization of epidermal growth factor/transforming growth factor- receptor on the human gastric mucasa.
Virchows Arch.
423:
57-63,
1993.
31.
Pandiella, A.,
and
J. Massague.
Cleavage of the membrane precursor for transforming growth factor is a regulated process.
Proc. Natl. Acad. Sci. USA
88:
1726-1730,
1991[Abstract].
32.
Polk, D. B. Epidermal growth factor
receptor-stimulated intestinal epithelial cell migration requires
phospholipase C activity.
Gastroenterology 114: 493-502,
33.
Rhodes, J. A.,
J. P. Tam,
U. Finke,
M. Saunders,
J. Bernanke,
W. Silen,
and
R. A. Murphy.
Transforming growth factor inhibits secretion of gastric acid.
Proc. Natl. Acad. Sci. USA
83:
3844-3846,
1986[Abstract].
34.
Rutten, M. J.,
P. J. Dempsey,
C. A. Luttropp,
M. A. Hawkey,
B. C. Sheppard,
R. A. Crass,
C. W. Deveney,
and
R. J. Coffey.
Identification of an EGF/TGF- receptor in primary cultures of guinea pig gastric mucous epithelial cells.
Am. J. Physiol.
270 (Gastrointest. Liver Physiol. 33):
G604-G612,
1996
35.
Sugiyama, N.,
Y. Tabuchi,
T. Horiuchi,
M. Obinata,
and
M. Furusawa.
Establishment of gastric surface mucous cell lines from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene.
Exp. Cell Res.
209:
382-387,
1993[Medline].
36.
Takemura, T.,
S. Kondo,
T. Homma,
M. Sakai,
and
R. C. Harris.
The membrane-bound from of heparin-binding epidermal growth factor-like growth factor promotes survival of cultured renal epithelial cells.
J. Biol. Chem.
272:
31036-31042,
1997
37.
Vey, M.,
W. Schafer,
S. Berhofer,
H.-D. Klenk,
and
W. Garten.
Maturation of the trans-Golgi network protease furin: compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation.
J. Cell Biol.
127:
1829-1842,
1994[Abstract].
38.
Wang, L.,
E. J. Wilson,
J. Osburn,
and
J. Del Valle.
Epidermal growth factor inhibits carbachol-stimulated canine parietal cell function via protein kinase C.
Gastroenterology
110:
469-477,
1996[Medline].