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• W2972040147 endingPage "15465" @default.
• W2972040147 startingPage "15446" @default.
• W2972040147 abstract "The tight junctional pore-forming protein claudin-2 (CLDN-2) mediates paracellular Na+ and water transport in leaky epithelia and alters cancer cell proliferation. Previously, we reported that tumor necrosis factor-α time-dependently alters CLDN-2 expression in tubular epithelial cells. Here, we found a similar expression pattern in a mouse kidney injury model (unilateral ureteral obstruction), consisting of an initial increase followed by a drop in CLDN-2 protein expression. CLDN-2 silencing in LLC-PK1 tubular cells induced activation and phosphorylation of guanine nucleotide exchange factor H1 (GEF-H1), leading to Ras homolog family member A (RHOA) activation. Silencing of other claudins had no such effects, and re-expression of an siRNA-resistant CLDN-2 prevented RHOA activation, indicating specific effects of CLDN-2 on RHOA. Moreover, kidneys from CLDN-2 knockout mice had elevated levels of active RHOA. Of note, CLDN-2 silencing reduced LLC-PK1 cell proliferation and elevated expression of cyclin-dependent kinase inhibitor P27 (P27KIP1) in a GEF-H1/RHOA-dependent manner. P27KIP1 silencing abrogated the effects of CLDN-2 depletion on proliferation. CLDN-2 loss also activated myocardin-related transcription factor (MRTF), a fibrogenic RHOA effector, and elevated expression of connective tissue growth factor and smooth muscle actin. Finally, CLDN-2 down-regulation contributed to RHOA activation and smooth muscle actin expression induced by prolonged tumor necrosis factor-α treatment, because they were mitigated by re-expression of CLDN-2. Our results indicate that CLDN-2 suppresses GEF-H1/RHOA. CLDN-2 down-regulation, for example, by inflammation, can reduce proliferation and promote MRTF activation through RHOA. These findings suggest that the initial CLDN-2 elevation might aid epithelial regeneration, and CLDN-2 loss could contribute to fibrotic reprogramming. The tight junctional pore-forming protein claudin-2 (CLDN-2) mediates paracellular Na+ and water transport in leaky epithelia and alters cancer cell proliferation. Previously, we reported that tumor necrosis factor-α time-dependently alters CLDN-2 expression in tubular epithelial cells. Here, we found a similar expression pattern in a mouse kidney injury model (unilateral ureteral obstruction), consisting of an initial increase followed by a drop in CLDN-2 protein expression. CLDN-2 silencing in LLC-PK1 tubular cells induced activation and phosphorylation of guanine nucleotide exchange factor H1 (GEF-H1), leading to Ras homolog family member A (RHOA) activation. Silencing of other claudins had no such effects, and re-expression of an siRNA-resistant CLDN-2 prevented RHOA activation, indicating specific effects of CLDN-2 on RHOA. Moreover, kidneys from CLDN-2 knockout mice had elevated levels of active RHOA. Of note, CLDN-2 silencing reduced LLC-PK1 cell proliferation and elevated expression of cyclin-dependent kinase inhibitor P27 (P27KIP1) in a GEF-H1/RHOA-dependent manner. P27KIP1 silencing abrogated the effects of CLDN-2 depletion on proliferation. CLDN-2 loss also activated myocardin-related transcription factor (MRTF), a fibrogenic RHOA effector, and elevated expression of connective tissue growth factor and smooth muscle actin. Finally, CLDN-2 down-regulation contributed to RHOA activation and smooth muscle actin expression induced by prolonged tumor necrosis factor-α treatment, because they were mitigated by re-expression of CLDN-2. Our results indicate that CLDN-2 suppresses GEF-H1/RHOA. CLDN-2 down-regulation, for example, by inflammation, can reduce proliferation and promote MRTF activation through RHOA. These findings suggest that the initial CLDN-2 elevation might aid epithelial regeneration, and CLDN-2 loss could contribute to fibrotic reprogramming." @default.
• W2972040147 created "2019-09-12" @default.
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• W2972040147 date "2019-10-01" @default.
• W2972040147 modified "2023-10-16" @default.
• W2972040147 title "Claudin-2 suppresses GEF-H1, RHOA, and MRTF, thereby impacting proliferation and profibrotic phenotype of tubular cells" @default.
• W2972040147 cites W1498232526 @default.
• W2972040147 cites W1522344314 @default.
• W2972040147 cites W1606848128 @default.
• W2972040147 cites W1903513044 @default.
• W2972040147 cites W191402491 @default.
• W2972040147 cites W1965699247 @default.
• W2972040147 cites W1970173720 @default.
• W2972040147 cites W1973623831 @default.
• W2972040147 cites W1980081948 @default.
• W2972040147 cites W1988824186 @default.
• W2972040147 cites W1989070672 @default.
• W2972040147 cites W1989506542 @default.
• W2972040147 cites W1992478515 @default.
• W2972040147 cites W1998086415 @default.
• W2972040147 cites W2002561949 @default.
• W2972040147 cites W2003275250 @default.
• W2972040147 cites W2007154580 @default.
• W2972040147 cites W2009455555 @default.
• W2972040147 cites W2011143322 @default.
• W2972040147 cites W2012998035 @default.
• W2972040147 cites W2016775639 @default.
• W2972040147 cites W2016979375 @default.
• W2972040147 cites W2018291032 @default.
• W2972040147 cites W2023687572 @default.
• W2972040147 cites W2024005495 @default.
• W2972040147 cites W2024726151 @default.
• W2972040147 cites W2029936621 @default.
• W2972040147 cites W2030070767 @default.
• W2972040147 cites W2030817968 @default.
• W2972040147 cites W2034955793 @default.
• W2972040147 cites W2036138598 @default.
• W2972040147 cites W2041614750 @default.
• W2972040147 cites W2048002893 @default.
• W2972040147 cites W2056700437 @default.
• W2972040147 cites W2057408402 @default.
• W2972040147 cites W2063266241 @default.
• W2972040147 cites W2066301699 @default.
• W2972040147 cites W2067045943 @default.
• W2972040147 cites W2069738597 @default.
• W2972040147 cites W2070439333 @default.
• W2972040147 cites W2072172421 @default.
• W2972040147 cites W2084142346 @default.
• W2972040147 cites W2085625787 @default.
• W2972040147 cites W2100483442 @default.
• W2972040147 cites W2101295963 @default.
• W2972040147 cites W2101547995 @default.
• W2972040147 cites W2104002497 @default.
• W2972040147 cites W2105487832 @default.
• W2972040147 cites W2108929354 @default.
• W2972040147 cites W2109355990 @default.
• W2972040147 cites W2111134333 @default.
• W2972040147 cites W2116119665 @default.
• W2972040147 cites W2116234513 @default.
• W2972040147 cites W2116701980 @default.
• W2972040147 cites W2119505108 @default.
• W2972040147 cites W2129236688 @default.
• W2972040147 cites W2132021216 @default.
• W2972040147 cites W2134292612 @default.
• W2972040147 cites W2136388349 @default.
• W2972040147 cites W2141425585 @default.
• W2972040147 cites W2143210637 @default.
• W2972040147 cites W2144668634 @default.
• W2972040147 cites W2148622416 @default.
• W2972040147 cites W2151834487 @default.
• W2972040147 cites W2153624387 @default.
• W2972040147 cites W2154589460 @default.
• W2972040147 cites W2160427528 @default.
• W2972040147 cites W2169328538 @default.
• W2972040147 cites W2170234615 @default.
• W2972040147 cites W2171188438 @default.
• W2972040147 cites W2270421398 @default.
• W2972040147 cites W2396646031 @default.
• W2972040147 cites W2405371629 @default.
• W2972040147 cites W2420944975 @default.
• W2972040147 cites W2469288120 @default.
• W2972040147 cites W2506244296 @default.
• W2972040147 cites W2557523423 @default.
• W2972040147 cites W2561217215 @default.
• W2972040147 cites W2561538587 @default.
• W2972040147 cites W2568334569 @default.
• W2972040147 cites W2605852828 @default.

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