Matches in SemOpenAlex for { <https://semopenalex.org/work/W4281731896> ?p ?o ?g. }
- W4281731896 abstract "Abstract Purpose Elevated transforming growth factor beta2 (TGFβ2) levels in the aqueous humor have been linked to glaucomatous outflow tissue dysfunction. Potential mediators of dysfunction are the transcriptional co-activators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ). However, the molecular underpinnings of YAP/TAZ modulation in Schlemm’s Canal (SC) cells under glaucomatous conditions are not well understood. Here, we investigate how TGFβ2 regulates YAP/TAZ activity in human SC (HSC) cells using biomimetic extracellular matrix (ECM) hydrogels, and examine whether pharmacologic YAP/TAZ inhibition would attenuate TGFβ2-induced HSC cell dysfunction. Methods Primary HSC cells were seeded atop photocrosslinked ECM hydrogels, made of collagen type I, elastin-like polypeptide and hyaluronic acid, or encapsulated within the hydrogels. HSC cells were induced with TGFβ2 in the absence or presence of concurrent actin destabilization or pharmacologic YAP/TAZ inhibition. Changes in actin cytoskeletal organization, YAP/TAZ activity, ECM production, phospho-myosin light chain levels, and hydrogel contraction were assessed. Results TGFβ2 significantly increased YAP/TAZ nuclear localization in HSC cells, which was prevented by either filamentous (F)-actin relaxation or depolymerization. Pharmacologic YAP/TAZ inhibition using verteporfin without light stimulation decreased fibronectin expression and reduced actomyosin cytoskeletal rearrangement in HSC cells induced by TGFβ2. Similarly, verteporfin significantly attenuated TGFβ2-induced HSC cell-encapsulated hydrogel contraction. Conclusions Our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions, and suggest that pharmacologic YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction." @default.
- W4281731896 created "2022-06-13" @default.
- W4281731896 creator A5004543881 @default.
- W4281731896 creator A5027515175 @default.
- W4281731896 creator A5055994625 @default.
- W4281731896 creator A5074673299 @default.
- W4281731896 creator A5080576283 @default.
- W4281731896 date "2022-06-06" @default.
- W4281731896 modified "2023-10-15" @default.
- W4281731896 title "YAP/TAZ mediate TGFβ2-induced Schlemm’s canal cell dysfunction" @default.
- W4281731896 cites W121305322 @default.
- W4281731896 cites W1442401682 @default.
- W4281731896 cites W1587940648 @default.
- W4281731896 cites W1599245394 @default.
- W4281731896 cites W1831697826 @default.
- W4281731896 cites W1966910690 @default.
- W4281731896 cites W1969258828 @default.
- W4281731896 cites W1970323907 @default.
- W4281731896 cites W1982541325 @default.
- W4281731896 cites W1983259922 @default.
- W4281731896 cites W1983785216 @default.
- W4281731896 cites W1986952803 @default.
- W4281731896 cites W1987657160 @default.
- W4281731896 cites W2004480757 @default.
- W4281731896 cites W2004722673 @default.
- W4281731896 cites W2007992196 @default.
- W4281731896 cites W2010748461 @default.
- W4281731896 cites W2027140863 @default.
- W4281731896 cites W2027779778 @default.
- W4281731896 cites W2028226574 @default.
- W4281731896 cites W2032731418 @default.
- W4281731896 cites W2036806537 @default.
- W4281731896 cites W2042130706 @default.
- W4281731896 cites W2047191461 @default.
- W4281731896 cites W2057266151 @default.
- W4281731896 cites W2060070915 @default.
- W4281731896 cites W2063394409 @default.
- W4281731896 cites W2065510468 @default.
- W4281731896 cites W2065896238 @default.
- W4281731896 cites W2073537216 @default.
- W4281731896 cites W2075625008 @default.
- W4281731896 cites W2077298757 @default.
- W4281731896 cites W2093683922 @default.
- W4281731896 cites W2099709490 @default.
- W4281731896 cites W2100641053 @default.
- W4281731896 cites W2102298863 @default.
- W4281731896 cites W2103894257 @default.
- W4281731896 cites W2106256269 @default.
- W4281731896 cites W2145192598 @default.
- W4281731896 cites W2146337514 @default.
- W4281731896 cites W2147321167 @default.
- W4281731896 cites W2160605010 @default.
- W4281731896 cites W2161491446 @default.
- W4281731896 cites W2232971833 @default.
- W4281731896 cites W2325896885 @default.
- W4281731896 cites W2405258106 @default.
- W4281731896 cites W2412930035 @default.
- W4281731896 cites W2523028783 @default.
- W4281731896 cites W2560035290 @default.
- W4281731896 cites W2593465390 @default.
- W4281731896 cites W2793740592 @default.
- W4281731896 cites W2799291895 @default.
- W4281731896 cites W2913470460 @default.
- W4281731896 cites W2938891495 @default.
- W4281731896 cites W3001856514 @default.
- W4281731896 cites W3020412742 @default.
- W4281731896 cites W3031489764 @default.
- W4281731896 cites W3049132659 @default.
- W4281731896 cites W3091732208 @default.
- W4281731896 cites W3096390470 @default.
- W4281731896 cites W3113309731 @default.
- W4281731896 cites W3129042037 @default.
- W4281731896 cites W3131963404 @default.
- W4281731896 cites W3135542256 @default.
- W4281731896 cites W3174682003 @default.
- W4281731896 cites W3198024241 @default.
- W4281731896 cites W4206045204 @default.
- W4281731896 cites W4220991506 @default.
- W4281731896 cites W4368144049 @default.
- W4281731896 cites W643118449 @default.
- W4281731896 doi "https://doi.org/10.1101/2022.06.06.494681" @default.
- W4281731896 hasPublicationYear "2022" @default.
- W4281731896 type Work @default.
- W4281731896 citedByCount "1" @default.
- W4281731896 countsByYear W42817318962022 @default.
- W4281731896 crossrefType "posted-content" @default.
- W4281731896 hasAuthorship W4281731896A5004543881 @default.
- W4281731896 hasAuthorship W4281731896A5027515175 @default.
- W4281731896 hasAuthorship W4281731896A5055994625 @default.
- W4281731896 hasAuthorship W4281731896A5074673299 @default.
- W4281731896 hasAuthorship W4281731896A5080576283 @default.
- W4281731896 hasBestOaLocation W42817318961 @default.
- W4281731896 hasConcept C118131993 @default.
- W4281731896 hasConcept C125705527 @default.
- W4281731896 hasConcept C142669718 @default.
- W4281731896 hasConcept C1491633281 @default.
- W4281731896 hasConcept C169760540 @default.
- W4281731896 hasConcept C172512520 @default.
- W4281731896 hasConcept C181104049 @default.
- W4281731896 hasConcept C185592680 @default.