Regulation of Cell Proliferation and Fluid Secretion in the Progressive Enlargement of Renal Cysts1

2015 ◽  
pp. 15-22 ◽  
Author(s):  
Jared J. Grantham
Keyword(s):  
Cell Proliferation ◽  
Fluid Secretion ◽  
Progressive Enlargement

Effects of DA-6034 on Aqueous Tear Fluid Secretion and Conjunctival Goblet Cell Proliferation

2009 ◽  
Vol 25 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Seul Min Choi ◽  
Yeong Geon Lee ◽  
Mi Jung Seo ◽  
Kyung Koo Kang ◽  
Byoung Ok Ahn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Goblet Cell ◽  
Fluid Secretion ◽  
Tear Fluid

scholarly journals cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells

2000 ◽  
Vol 11 (7) ◽  
pp. 1179-1187 ◽  
Author(s):  
KAZUSHIGE HANAOKA ◽  
WILLIAM B. GUGGINO
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Kidney Disease ◽  
Epidermal Growth Factor ◽  
Fluid Secretion ◽  
Cyst Formation ◽  
Polycystic Kidney ◽  
Epidermal Growth ◽  
Cyst Growth

Abstract. Both epithelial cell proliferation and fluid accumulation are responsible for cyst growth in autosomal dominant polycystic kidney disease (ADPKD). It was previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in cysts from ADPKD patients and suggested that cAMP-stimulated Cl-and fluid secretion occurs through CFTR. The purpose of this study was to investigate the role of cell proliferation in cyst formation in ADPKD and to explore further the role of fluid secretion in cyst growth. Primary cultures both of ADPKD epithelial cells and a mixed population of normal renal epithelial cells isolated from the cortex (HRCE cells) were used. This study tested whether cAMP was involved both in stimulating cell proliferation and formation of cystsin vitro.3H-Thymidine incorporation assays showed that epidermal growth factor stimulated proliferation both in ADPKD cells and HRCE cells. In addition, cAMP stimulated DNA synthesis and cell proliferation in ADPKD, but not HRCE, cells. The effects of cAMP and epidermal growth factor on cell growth in ADPKD cells were additive. cAMP also stimulated cyst enlargement and fluid secretion in ADPKD cells. By contrast, cyst formation and enlargement from HRCE cells occurred without cAMP. Fluid secretion into the cyst lumen was blocked by diphenylamine carboxylic acid (DPC) and glibenclamide in ADPKD cells but blocked only by DPC in HRCE cells. This study showed that ADPKD cells have unique characteristics ; cAMP stimulates fluid secretion and cell proliferation, indicating cAMP plays a very important role in cyst growth during the course of ADPKD.

scholarly journals Chemical modification of cell proliferation and fluid secretion in renal cysts

1989 ◽  
Vol 35 (6) ◽  
pp. 1379-1389 ◽  
Author(s):  
Jared J. Grantham ◽  
Marie Uchic ◽  
E.J. Cragoe ◽  
James Kornhaus ◽  
J. Aaron Grantham ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Chemical Modification ◽  
Renal Cysts ◽  
Fluid Secretion

scholarly journals Tolvaptan inhibits ERK-dependent cell proliferation, Cl− secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin

2011 ◽  
Vol 301 (5) ◽  
pp. F1005-F1013 ◽  
Author(s):  
Gail A. Reif ◽  
Tamio Yamaguchi ◽  
Emily Nivens ◽  
Hiroyuki Fujiki ◽  
Cibele S. Pinto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Short Circuit ◽  
Three Dimensional ◽  
Short Circuit Current ◽  
Collagen Matrix ◽  
Fluid Secretion ◽  
Intracellular Camp ◽  
Erk Activity ◽  
Cyst Growth

In autosomal dominant polycystic kidney disease (ADPKD), arginine vasopressin (AVP) accelerates cyst growth by stimulating cAMP-dependent ERK activity and epithelial cell proliferation and by promoting Cl−-dependent fluid secretion. Tolvaptan, a V2 receptor antagonist, inhibits the renal effects of AVP and slows cyst growth in PKD animals. Here, we determined the effect of graded concentrations of tolvaptan on intracellular cAMP, ERK activity, cell proliferation, and transcellular Cl− secretion using human ADPKD cyst epithelial cells. Incubation of ADPKD cells with 10−9 M AVP increased intracellular cAMP and stimulated ERK and cell proliferation. Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC50 of ∼10−10 M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation. Basolateral application of AVP to ADPKD cell monolayers grown on permeable supports caused a sustained increase in short-circuit current that was completely blocked by the Cl− channel blocker CFTRinh-172, consistent with AVP-induced transepithelial Cl− secretion. Tolvaptan inhibited AVP-induced Cl− secretion and decreased in vitro cyst growth of ADPKD cells cultured within a three-dimensional collagen matrix. These data demonstrate that relatively low concentrations of tolvaptan inhibit AVP-stimulated cell proliferation and Cl−-dependent fluid secretion by human ADPKD cystic cells.

scholarly journals CCK-, secretin-, and cholinergic-independent pancreatic fluid hypersecretion in protease inhibitor-treated rats

1998 ◽  
Vol 274 (2) ◽  
pp. G406-G412 ◽  
Author(s):  
Mitsuyoshi Yamamoto ◽  
Hisashi Shirohara ◽  
Makoto Otsuki
Keyword(s):  
Cell Proliferation ◽  
Oral Administration ◽  
Protease Inhibitor ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Pancreatic Fluid ◽  
Single Oral Administration ◽  
Plasma Cholecystokinin ◽  
Active Proliferation

Plasma cholecystokinin (CCK) levels in fed rats increased from 2.59 ± 0.13 pmol/l to the peak of 27.6 ± 4.1 pmol/l at 1 h after a single oral administration of synthetic protease inhibitor (PI; ethyl N-allyl- N-{( E)-2-methyl-3-[4-(4-amidino-phenoxycarbonyl)phenyl]propenoyl}amino acetate methansulfonate; 20 mg/kg body wt), but then returned to the preloading value at 12 h after administration. The pancreatic fluid secretion, rich in chloride but poor in bicarbonate, was significantly elevated at 6–12 h postfeeding (100.9 ± 8.2 vs. 27.3 ± 2.3 μl/30 min in control rats, P < 0.01). Loxiglumide (50 mg ⋅ kg body wt−1 ⋅ h−1), atropine (100 μg ⋅ kg body wt−1 ⋅ h−1), or antisecretin serum (100 μl/rat) at 12 h postfeeding did not modify the fluid hypersecretion. Loxiglumide, when given together with PI, completely abolished fluid hypersecretion, but it could not inhibit hypersecretion when applied 3 h after PI treatment. Labeling with 5-bromo-2′-deoxyuridine showed active proliferation of acinar cells at 3 h after PI treatment (3.56 ± 0.29% vs. 0.46 ± 0.08% in control, P < 0.001), but not in rats given loxiglumide together with PI. In rats that fasted from 12 h before to 12 h after PI feeding, neither pancreatic fluid hypersecretion nor active proliferation of acinar cells was observed. These results suggest that pancreatic fluid hypersecretion in fed rats at 6–12 h after PI treatment is caused not by CCK-, secretin-, or cholinergic-dependent mechanisms but probably by acinar cell proliferation.

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