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• W3100343205 endingPage "108362" @default.
• W3100343205 startingPage "108362" @default.
• W3100343205 abstract "The transformation of quiescent keratocytes to activated fibroblasts and myofibroblasts (KFM transformation) largely depends on transforming growth factor beta (TGFβ) signaling. Initiation of the TGFβ signaling cascade results from binding of TGFβ to the labile type I TGFβ receptor (TGFβRI), which is stabilized by the 90 kDa heat shock protein (Hsp90). Since myofibroblast persistence within the corneal stroma can result in stromal haze and corneal fibrosis in patients undergoing keratorefractive therapy, modulation of TGFβ signaling through Hsp90 inhibition would represent a novel approach to prevent myofibroblast persistence. In vitro, rabbit corneal fibroblasts (RCFs) or stratified immortalized human corneal epithelial cells (hTCEpi) were treated with a Hsp90 inhibitor (17AAG) in the presence/absence of TGFβ1. RCFs were cultured either on tissue culture plastic, anisotropically patterned substrates, and hydrogels of varying stiffness. Cellular responses to both cytoactive and variable substrates were assessed by morphologic changes to the cells, and alterations in expression patterns of key keratocyte and myofibroblast proteins using PCR, Western blotting and immunocytochemistry. Transepithelial electrical resistance (TEER) measurements were performed to establish epithelial barrier integrity. In vivo, the corneas of New Zealand White rabbits were wounded by phototherapeutic keratectomy (PTK) and treated with 17AAG (3× or 6× daily) either immediately or 7 days after wounding for 28 days. Rabbits underwent clinical ophthalmic examinations, SPOTS scoring and advanced imaging on days 0, 1, 3, 7, 10, 14, 21 and 28. On day 28, rabbits were euthanized and histopathology/immunohistochemistry was performed. In vitro data demonstrated that 17AAG inhibited KFM transformation with the de-differentiation of spindle shaped myofibroblasts to dendritic keratocyte-like cells accompanied by significant upregulation of corneal crystallins and suppression of myofibroblast markers regardless of TGFβ1 treatment. RCFs cultured on soft hydrogels or patterned substrates exhibited elevated expression of α-smooth muscle actin (αSMA) in the presence of 17AAG. Treatment of hTCEpi cells disrupted zonula occludens 1 (ZO-1) adherens junction formation. In vivo, there were no differences detected in nearly all clinical parameters assessed between treatment groups. However, rabbits treated with 17AAG developed greater stromal haze formation compared with controls, irrespective of frequency of administration. Lastly, there was increased αSMA positive myofibroblasts in the stroma of 17AAG treated animals when compared with controls. Hsp90 inhibition promoted reversion of the myofibroblast to keratocyte phenotype, although this only occurred on rigid substrates. By contrast, in vivo Hsp90 inhibition was detrimental to corneal wound healing likely due to impairment in corneal epithelial closure and barrier function restoration. Collectively, our data demonstrated a strong interplay in vitro between biophysical cues and soluble signaling molecules in determining corneal stromal cell phenotype." @default.
• W3100343205 created "2020-11-23" @default.
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• W3100343205 date "2021-01-01" @default.
• W3100343205 modified "2023-09-27" @default.
• W3100343205 title "Differential effects of Hsp90 inhibition on corneal cells in vitro and in vivo" @default.
• W3100343205 cites W1485161887 @default.
• W3100343205 cites W1503480585 @default.
• W3100343205 cites W1508331875 @default.
• W3100343205 cites W15541802 @default.
• W3100343205 cites W1554444859 @default.
• W3100343205 cites W1580831370 @default.
• W3100343205 cites W1607703534 @default.
• W3100343205 cites W1963892111 @default.
• W3100343205 cites W1968893406 @default.
• W3100343205 cites W1973540550 @default.
• W3100343205 cites W1977649843 @default.
• W3100343205 cites W1979746030 @default.
• W3100343205 cites W1986532418 @default.
• W3100343205 cites W1988933621 @default.
• W3100343205 cites W1989532138 @default.
• W3100343205 cites W1993066239 @default.
• W3100343205 cites W1993350514 @default.
• W3100343205 cites W1997105607 @default.
• W3100343205 cites W1997214631 @default.
• W3100343205 cites W1998746760 @default.
• W3100343205 cites W2004163365 @default.
• W3100343205 cites W2008111880 @default.
• W3100343205 cites W2008389295 @default.
• W3100343205 cites W2010422325 @default.
• W3100343205 cites W2022215414 @default.
• W3100343205 cites W2022973321 @default.
• W3100343205 cites W2023288701 @default.
• W3100343205 cites W2028237347 @default.
• W3100343205 cites W2030589581 @default.
• W3100343205 cites W2031870183 @default.
• W3100343205 cites W2037658248 @default.
• W3100343205 cites W2038814746 @default.
• W3100343205 cites W2040106948 @default.
• W3100343205 cites W2041218201 @default.
• W3100343205 cites W2042699875 @default.
• W3100343205 cites W2050621039 @default.
• W3100343205 cites W2052753852 @default.
• W3100343205 cites W2055626914 @default.
• W3100343205 cites W2059717168 @default.
• W3100343205 cites W2066947166 @default.
• W3100343205 cites W2067933702 @default.
• W3100343205 cites W2070741283 @default.
• W3100343205 cites W2071362471 @default.
• W3100343205 cites W2072566967 @default.
• W3100343205 cites W2072827131 @default.
• W3100343205 cites W2076933760 @default.
• W3100343205 cites W2080268492 @default.
• W3100343205 cites W2085060090 @default.
• W3100343205 cites W2085072359 @default.
• W3100343205 cites W2086989629 @default.
• W3100343205 cites W2091047889 @default.
• W3100343205 cites W2092972935 @default.
• W3100343205 cites W2094060804 @default.
• W3100343205 cites W2096955693 @default.
• W3100343205 cites W2104061566 @default.
• W3100343205 cites W2113523455 @default.
• W3100343205 cites W2114918609 @default.
• W3100343205 cites W2120729063 @default.
• W3100343205 cites W2121099175 @default.
• W3100343205 cites W2122933644 @default.
• W3100343205 cites W2123956706 @default.
• W3100343205 cites W2125691179 @default.
• W3100343205 cites W2127609119 @default.
• W3100343205 cites W2129004089 @default.
• W3100343205 cites W2131728593 @default.
• W3100343205 cites W2133147961 @default.
• W3100343205 cites W2148566823 @default.
• W3100343205 cites W2151878020 @default.
• W3100343205 cites W2162225623 @default.
• W3100343205 cites W2164530918 @default.
• W3100343205 cites W2175029576 @default.
• W3100343205 cites W2179244018 @default.
• W3100343205 cites W2219429396 @default.
• W3100343205 cites W2284077772 @default.
• W3100343205 cites W2284389943 @default.
• W3100343205 cites W2326492036 @default.
• W3100343205 cites W2410596019 @default.
• W3100343205 cites W2417920442 @default.
• W3100343205 cites W2604863264 @default.

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