Matches in SemOpenAlex for { <https://semopenalex.org/work/W2920935501> ?p ?o ?g. }
- W2920935501 abstract "Abstract Epithelial injury is a key initiator of fibrosis but - in contrast to the previous paradigm - the epithelium in situ does not undergo wide-spread epithelial-mesenchymal/myofibroblast transition (EMT/EMyT). Instead, it assumes a Profibrotic Epithelial Phenotype (PEP) characterized by fibrogenic cytokine production. The transcriptional mechanisms underlying PEP are undefined. As we have shown that two RhoA/cytoskeleton-regulated transcriptional coactivators, Myocardin-related transcription factor (MRTF) and TAZ, are indispensable for EMyT, we asked if they might mediate PEP as well. Here we show that mechanical stress (cyclic stretch) increased the expression of transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), platelet-derived growth factor and Indian Hedgehog mRNA in LLC-PK1 tubular cells. These responses were mitigated by siRNA-mediated silencing or pharmacological inhibition of MRTF (CCG-1423) or TAZ (verteporfin). RhoA inhibition exerted similar effects. Unilateral ureteral obstruction, a murine model of mechanically-triggered kidney fibrosis, induced tubular RhoA activation along with overexpression/nuclear accumulation of MRTF and TAZ, and increased transcription of the above-mentioned cytokines. Laser capture microdissection revealed TAZ, TGFβ1 and CTGF induction specifically in the tubular epithelium. CCG-1423 suppressed total renal and tubular expression of these proteins. Thus, MRTF regulates epithelial TAZ expression, and both MRTF and TAZ are critical mediators of PEP-related epithelial cytokine production." @default.
- W2920935501 created "2019-03-22" @default.
- W2920935501 creator A5001912709 @default.
- W2920935501 creator A5004819829 @default.
- W2920935501 creator A5008022917 @default.
- W2920935501 creator A5015579145 @default.
- W2920935501 creator A5029172497 @default.
- W2920935501 creator A5036345848 @default.
- W2920935501 creator A5046643104 @default.
- W2920935501 creator A5055198525 @default.
- W2920935501 creator A5075363316 @default.
- W2920935501 creator A5086761442 @default.
- W2920935501 creator A5087869067 @default.
- W2920935501 date "2019-03-13" @default.
- W2920935501 modified "2023-10-18" @default.
- W2920935501 title "Profibrotic epithelial phenotype: a central role for MRTF and TAZ" @default.
- W2920935501 cites W1215049722 @default.
- W2920935501 cites W1505584712 @default.
- W2920935501 cites W1966760994 @default.
- W2920935501 cites W1969882218 @default.
- W2920935501 cites W1976433874 @default.
- W2920935501 cites W1976996489 @default.
- W2920935501 cites W1982498121 @default.
- W2920935501 cites W1982976290 @default.
- W2920935501 cites W1987844828 @default.
- W2920935501 cites W1988824186 @default.
- W2920935501 cites W1996573964 @default.
- W2920935501 cites W1997088049 @default.
- W2920935501 cites W2001517178 @default.
- W2920935501 cites W2003275250 @default.
- W2920935501 cites W2007821852 @default.
- W2920935501 cites W2011346718 @default.
- W2920935501 cites W2013572062 @default.
- W2920935501 cites W2018079417 @default.
- W2920935501 cites W2018981570 @default.
- W2920935501 cites W2021017423 @default.
- W2920935501 cites W2021448292 @default.
- W2920935501 cites W2026733880 @default.
- W2920935501 cites W2041614750 @default.
- W2920935501 cites W2044982400 @default.
- W2920935501 cites W2050053473 @default.
- W2920935501 cites W2052092179 @default.
- W2920935501 cites W2053512383 @default.
- W2920935501 cites W2058357630 @default.
- W2920935501 cites W2065589175 @default.
- W2920935501 cites W2068050227 @default.
- W2920935501 cites W2090392605 @default.
- W2920935501 cites W2093723806 @default.
- W2920935501 cites W2098977806 @default.
- W2920935501 cites W2100429415 @default.
- W2920935501 cites W2100641053 @default.
- W2920935501 cites W2102490423 @default.
- W2920935501 cites W2104002497 @default.
- W2920935501 cites W2106887481 @default.
- W2920935501 cites W2109221701 @default.
- W2920935501 cites W2114051326 @default.
- W2920935501 cites W2116119665 @default.
- W2920935501 cites W2119505108 @default.
- W2920935501 cites W2123233663 @default.
- W2920935501 cites W2126463670 @default.
- W2920935501 cites W2129055432 @default.
- W2920935501 cites W2129236688 @default.
- W2920935501 cites W2139602514 @default.
- W2920935501 cites W2141425585 @default.
- W2920935501 cites W2141700579 @default.
- W2920935501 cites W2146239575 @default.
- W2920935501 cites W2146337514 @default.
- W2920935501 cites W2146434832 @default.
- W2920935501 cites W2151260549 @default.
- W2920935501 cites W2156935689 @default.
- W2920935501 cites W2158458517 @default.
- W2920935501 cites W2166899649 @default.
- W2920935501 cites W2167279371 @default.
- W2920935501 cites W2167978765 @default.
- W2920935501 cites W2168072233 @default.
- W2920935501 cites W2170143992 @default.
- W2920935501 cites W2175620885 @default.
- W2920935501 cites W2189664213 @default.
- W2920935501 cites W2204732867 @default.
- W2920935501 cites W2208280515 @default.
- W2920935501 cites W2219743938 @default.
- W2920935501 cites W2223084608 @default.
- W2920935501 cites W2223413920 @default.
- W2920935501 cites W2286829789 @default.
- W2920935501 cites W2295717665 @default.
- W2920935501 cites W2340544421 @default.
- W2920935501 cites W2400949487 @default.
- W2920935501 cites W2401751910 @default.
- W2920935501 cites W2411483269 @default.
- W2920935501 cites W2507196425 @default.
- W2920935501 cites W2508686416 @default.
- W2920935501 cites W2541359632 @default.
- W2920935501 cites W2560115947 @default.
- W2920935501 cites W2587871077 @default.
- W2920935501 cites W2592025222 @default.
- W2920935501 cites W2592974986 @default.
- W2920935501 cites W2600392992 @default.
- W2920935501 cites W2605766014 @default.
- W2920935501 cites W2606475770 @default.
- W2920935501 cites W2621172390 @default.