Matches in SemOpenAlex for { <https://semopenalex.org/work/W2937290574> ?p ?o ?g. }
- W2937290574 abstract "Fibrosis is a hallmark in the pathogenesis of various diseases, with very limited therapeutic solutions. A key event in the fibrotic process is the expression of contractile proteins, including α-smooth muscle actin (αSMA) by fibroblasts, which become myofibroblasts. Here, we report the results of a high-throughput screening of a library of approved drugs that led to the discovery of haloperidol, a common antipsychotic drug, as a potent inhibitor of myofibroblast activation. We show that haloperidol exerts its antifibrotic effect on primary murine and human fibroblasts by binding to sigma receptor 1, independent from the canonical transforming growth factor-β signaling pathway. Its mechanism of action involves the modulation of intracellular calcium, with moderate induction of endoplasmic reticulum stress response, which in turn abrogates Notch1 signaling and the consequent expression of its targets, including αSMA. Importantly, haloperidol also reduced the fibrotic burden in 3 different animal models of lung, cardiac, and tumor-associated fibrosis, thus supporting the repurposing of this drug for the treatment of fibrotic conditions." @default.
- W2937290574 created "2019-04-25" @default.
- W2937290574 creator A5006044124 @default.
- W2937290574 creator A5011730524 @default.
- W2937290574 creator A5017943087 @default.
- W2937290574 creator A5022450686 @default.
- W2937290574 creator A5025917999 @default.
- W2937290574 creator A5026564872 @default.
- W2937290574 creator A5029345828 @default.
- W2937290574 creator A5035147964 @default.
- W2937290574 creator A5035936838 @default.
- W2937290574 creator A5038230299 @default.
- W2937290574 creator A5043471682 @default.
- W2937290574 creator A5045833196 @default.
- W2937290574 creator A5046467955 @default.
- W2937290574 creator A5049910153 @default.
- W2937290574 creator A5056221917 @default.
- W2937290574 creator A5058620782 @default.
- W2937290574 creator A5065373709 @default.
- W2937290574 creator A5066779291 @default.
- W2937290574 creator A5067891852 @default.
- W2937290574 creator A5069332095 @default.
- W2937290574 creator A5070165519 @default.
- W2937290574 creator A5074125267 @default.
- W2937290574 creator A5091060786 @default.
- W2937290574 date "2019-04-18" @default.
- W2937290574 modified "2023-10-01" @default.
- W2937290574 title "High-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation" @default.
- W2937290574 cites W1593385535 @default.
- W2937290574 cites W1695278265 @default.
- W2937290574 cites W1851183333 @default.
- W2937290574 cites W1964002372 @default.
- W2937290574 cites W1966920422 @default.
- W2937290574 cites W1970919811 @default.
- W2937290574 cites W1972494520 @default.
- W2937290574 cites W1985588649 @default.
- W2937290574 cites W1986542470 @default.
- W2937290574 cites W1992726552 @default.
- W2937290574 cites W2000065998 @default.
- W2937290574 cites W2002439304 @default.
- W2937290574 cites W2004630162 @default.
- W2937290574 cites W2007838869 @default.
- W2937290574 cites W2008540717 @default.
- W2937290574 cites W2009423060 @default.
- W2937290574 cites W2012993485 @default.
- W2937290574 cites W2015568641 @default.
- W2937290574 cites W2015851393 @default.
- W2937290574 cites W2019079031 @default.
- W2937290574 cites W2026638336 @default.
- W2937290574 cites W2047453275 @default.
- W2937290574 cites W2048355238 @default.
- W2937290574 cites W2050666972 @default.
- W2937290574 cites W2051788770 @default.
- W2937290574 cites W2054604628 @default.
- W2937290574 cites W2054814217 @default.
- W2937290574 cites W2056716376 @default.
- W2937290574 cites W2065145954 @default.
- W2937290574 cites W2077142292 @default.
- W2937290574 cites W2082414464 @default.
- W2937290574 cites W2088724129 @default.
- W2937290574 cites W2092224692 @default.
- W2937290574 cites W2096280264 @default.
- W2937290574 cites W2101640321 @default.
- W2937290574 cites W2102941647 @default.
- W2937290574 cites W2105699441 @default.
- W2937290574 cites W2107640420 @default.
- W2937290574 cites W2110452002 @default.
- W2937290574 cites W2113596764 @default.
- W2937290574 cites W2116043657 @default.
- W2937290574 cites W2116645811 @default.
- W2937290574 cites W2127031103 @default.
- W2937290574 cites W2128489958 @default.
- W2937290574 cites W2131519133 @default.
- W2937290574 cites W2137662702 @default.
- W2937290574 cites W2137796176 @default.
- W2937290574 cites W2139554920 @default.
- W2937290574 cites W2139568257 @default.
- W2937290574 cites W2140546989 @default.
- W2937290574 cites W2143723854 @default.
- W2937290574 cites W2157358346 @default.
- W2937290574 cites W2159036727 @default.
- W2937290574 cites W2159415118 @default.
- W2937290574 cites W2161548283 @default.
- W2937290574 cites W2164134225 @default.
- W2937290574 cites W2166874505 @default.
- W2937290574 cites W2167484211 @default.
- W2937290574 cites W2169439644 @default.
- W2937290574 cites W2171499163 @default.
- W2937290574 cites W2172060727 @default.
- W2937290574 cites W2172121723 @default.
- W2937290574 cites W2172160531 @default.
- W2937290574 cites W2172579382 @default.
- W2937290574 cites W2192080449 @default.
- W2937290574 cites W2224214468 @default.
- W2937290574 cites W2270186097 @default.
- W2937290574 cites W2294946349 @default.
- W2937290574 cites W2314811232 @default.
- W2937290574 cites W2342479713 @default.
- W2937290574 cites W2347012456 @default.
- W2937290574 cites W2414453316 @default.