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- W2750640253 abstract "Scarring and fibrotic disease result from the persistence of myofibroblasts characterized by high surface expression of αv integrins and subsequent activation of TGFβ, however the mechanism controlling their surface abundance is unknown. Genetic screening revealed that human primary stromal corneal myofibroblasts overexpress a subset of deubiquitinating enzymes (DUBs), which remove ubiquitin from proteins, preventing degradation. Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins β1 and β5 in cell lysates whereas recombinant USP10 removes ubiquitin from these integrin subunits. Correspondingly, the loss and gain of USP10 decreases and increases, respectively αv/β1/β5 protein levels, without altering gene expression. Consequently, endogenous TGFβ is activated and the fibrotic markers alpha-smooth muscle actin (α-SMA) and cellular fibronectin (FN-EDA) are induced. Blocking either TGFβ signaling or cell-surface αv integrins after USP10 overexpression prevents or reduces fibrotic marker expression. Finally, silencing of USP10 in an ex-vivo cornea organ culture model prevents the induction of fibrotic markers and promotes regenerative healing. This novel mechanism puts DUB expression at the head of a cascade regulating integrin abundance and suggests USP10 as a novel anti-fibrotic target." @default.
- W2750640253 created "2017-09-15" @default.
- W2750640253 creator A5013283544 @default.
- W2750640253 creator A5042139243 @default.
- W2750640253 creator A5078480588 @default.
- W2750640253 creator A5085275525 @default.
- W2750640253 date "2017-01-01" @default.
- W2750640253 modified "2023-09-25" @default.
- W2750640253 title "The deubiquitinase USP10 regulates integrin beta1 and beta5 and fibrotic wound healing" @default.
- W2750640253 cites W1526201307 @default.
- W2750640253 cites W1543126301 @default.
- W2750640253 cites W1550251860 @default.
- W2750640253 cites W1551233310 @default.
- W2750640253 cites W1607291301 @default.
- W2750640253 cites W1677186713 @default.
- W2750640253 cites W1948640476 @default.
- W2750640253 cites W1964365041 @default.
- W2750640253 cites W1965253007 @default.
- W2750640253 cites W1965576964 @default.
- W2750640253 cites W1967922151 @default.
- W2750640253 cites W1969576458 @default.
- W2750640253 cites W1975654228 @default.
- W2750640253 cites W1977347307 @default.
- W2750640253 cites W1981465541 @default.
- W2750640253 cites W1988225483 @default.
- W2750640253 cites W1989591249 @default.
- W2750640253 cites W1991095357 @default.
- W2750640253 cites W1995592152 @default.
- W2750640253 cites W1998351838 @default.
- W2750640253 cites W2003709426 @default.
- W2750640253 cites W2010045652 @default.
- W2750640253 cites W2010703227 @default.
- W2750640253 cites W2013537969 @default.
- W2750640253 cites W2014067185 @default.
- W2750640253 cites W2016996307 @default.
- W2750640253 cites W2020317906 @default.
- W2750640253 cites W2021165493 @default.
- W2750640253 cites W2022491847 @default.
- W2750640253 cites W2026318673 @default.
- W2750640253 cites W2027875827 @default.
- W2750640253 cites W2032609555 @default.
- W2750640253 cites W2033055043 @default.
- W2750640253 cites W2034338127 @default.
- W2750640253 cites W2043003164 @default.
- W2750640253 cites W2052443410 @default.
- W2750640253 cites W2055614158 @default.
- W2750640253 cites W2056029035 @default.
- W2750640253 cites W2062575712 @default.
- W2750640253 cites W2068905490 @default.
- W2750640253 cites W2070315522 @default.
- W2750640253 cites W2072981065 @default.
- W2750640253 cites W2076978295 @default.
- W2750640253 cites W2078954749 @default.
- W2750640253 cites W2086735491 @default.
- W2750640253 cites W2087347093 @default.
- W2750640253 cites W2090765436 @default.
- W2750640253 cites W2094536853 @default.
- W2750640253 cites W2096346259 @default.
- W2750640253 cites W2101858316 @default.
- W2750640253 cites W2105013496 @default.
- W2750640253 cites W2105231460 @default.
- W2750640253 cites W2106969933 @default.
- W2750640253 cites W2109511371 @default.
- W2750640253 cites W2110272715 @default.
- W2750640253 cites W2114317477 @default.
- W2750640253 cites W2117697996 @default.
- W2750640253 cites W2121701455 @default.
- W2750640253 cites W2122104511 @default.
- W2750640253 cites W2123179922 @default.
- W2750640253 cites W2127537635 @default.
- W2750640253 cites W2127964575 @default.
- W2750640253 cites W2131884119 @default.
- W2750640253 cites W2131950257 @default.
- W2750640253 cites W2138164563 @default.
- W2750640253 cites W2141768942 @default.
- W2750640253 cites W2144449878 @default.
- W2750640253 cites W2147719913 @default.
- W2750640253 cites W2151381771 @default.
- W2750640253 cites W2154195761 @default.
- W2750640253 cites W2159360181 @default.
- W2750640253 cites W2163446421 @default.
- W2750640253 cites W2165688553 @default.
- W2750640253 cites W2168708680 @default.
- W2750640253 cites W2168854378 @default.
- W2750640253 cites W2172043646 @default.
- W2750640253 cites W2172090615 @default.
- W2750640253 cites W2172115229 @default.
- W2750640253 cites W2297079667 @default.
- W2750640253 cites W2316971333 @default.
- W2750640253 cites W232770196 @default.
- W2750640253 cites W2345156168 @default.
- W2750640253 cites W2438056774 @default.
- W2750640253 cites W2510413241 @default.
- W2750640253 cites W2524727464 @default.
- W2750640253 cites W2580231811 @default.
- W2750640253 cites W2590253705 @default.
- W2750640253 cites W2918086501 @default.
- W2750640253 doi "https://doi.org/10.1242/jcs.204628" @default.
- W2750640253 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5665446" @default.
- W2750640253 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28851806" @default.