FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2840834498> ?p ?o ?g. }

• W2840834498 abstract "Persistent fibrosis in multiple organs is the hallmark of systemic sclerosis (SSc). Recent genetic and genomic studies implicate TLRs and their damage-associated molecular pattern (DAMP) endogenous ligands in fibrosis. To test the hypothesis that TLR4 and its coreceptor myeloid differentiation 2 (MD2) drive fibrosis persistence, we measured MD2/TLR4 signaling in tissues from patients with fibrotic SSc, and we examined the impact of MD2 targeting using a potentially novel small molecule. Levels of MD2 and TLR4, and a TLR4-responsive gene signature, were enhanced in SSc skin biopsies. We developed a small molecule that selectively blocks MD2, which is uniquely required for TLR4 signaling. Targeting MD2/TLR4 abrogated inducible and constitutive myofibroblast transformation and matrix remodeling in fibroblast monolayers, as well as in 3-D scleroderma skin equivalents and human skin explants. Moreover, the selective TLR4 inhibitor prevented organ fibrosis in several preclinical disease models and mouse strains, and it reversed preexisting fibrosis. Fibroblast-specific deletion of TLR4 in mice afforded substantial protection from skin and lung fibrosis. By comparing experimentally generated fibroblast TLR4 gene signatures with SSc skin biopsy gene expression datasets, we identified a subset of SSc patients displaying an activated TLR4 signature. Together, results from these human and mouse studies implicate MD2/TLR4-dependent fibroblast activation as a key driver of persistent organ fibrosis. The results suggest that SSc patients with high TLR4 activity might show optimal therapeutic response to selective inhibitors of MD2/TLR4 complex formation." @default.
• W2840834498 created "2018-07-19" @default.
• W2840834498 creator A5012539047 @default.
• W2840834498 creator A5012966437 @default.
• W2840834498 creator A5018394997 @default.
• W2840834498 creator A5022178148 @default.
• W2840834498 creator A5025581121 @default.
• W2840834498 creator A5029005602 @default.
• W2840834498 creator A5043151851 @default.
• W2840834498 creator A5053041403 @default.
• W2840834498 creator A5056632481 @default.
• W2840834498 creator A5058057676 @default.
• W2840834498 creator A5068704522 @default.
• W2840834498 creator A5069895972 @default.
• W2840834498 creator A5073206138 @default.
• W2840834498 date "2018-07-12" @default.
• W2840834498 modified "2023-10-12" @default.
• W2840834498 title "TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung" @default.
• W2840834498 cites W133811466 @default.
• W2840834498 cites W1516788544 @default.
• W2840834498 cites W1588127651 @default.
• W2840834498 cites W1705692489 @default.
• W2840834498 cites W1966676847 @default.
• W2840834498 cites W1976505464 @default.
• W2840834498 cites W1983175066 @default.
• W2840834498 cites W1983419107 @default.
• W2840834498 cites W1988795126 @default.
• W2840834498 cites W2003214809 @default.
• W2840834498 cites W2004534466 @default.
• W2840834498 cites W2011393692 @default.
• W2840834498 cites W2015823745 @default.
• W2840834498 cites W2019141144 @default.
• W2840834498 cites W2024866056 @default.
• W2840834498 cites W20377036 @default.
• W2840834498 cites W2041250281 @default.
• W2840834498 cites W2045142779 @default.
• W2840834498 cites W2053189438 @default.
• W2840834498 cites W2058357630 @default.
• W2840834498 cites W2060122053 @default.
• W2840834498 cites W2088018826 @default.
• W2840834498 cites W2095833996 @default.
• W2840834498 cites W2109491705 @default.
• W2840834498 cites W2111738460 @default.
• W2840834498 cites W2125874167 @default.
• W2840834498 cites W2130655121 @default.
• W2840834498 cites W2134557327 @default.
• W2840834498 cites W2152256753 @default.
• W2840834498 cites W2153105134 @default.
• W2840834498 cites W2154382529 @default.
• W2840834498 cites W2164906049 @default.
• W2840834498 cites W2165876096 @default.
• W2840834498 cites W2166007002 @default.
• W2840834498 cites W2172055711 @default.
• W2840834498 cites W2177675794 @default.
• W2840834498 cites W2411779324 @default.
• W2840834498 cites W2475933914 @default.
• W2840834498 cites W2527737932 @default.
• W2840834498 cites W2595556343 @default.
• W2840834498 cites W2612060684 @default.
• W2840834498 doi "https://doi.org/10.1172/jci.insight.98850" @default.
• W2840834498 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6124522" @default.
• W2840834498 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29997297" @default.
• W2840834498 hasPublicationYear "2018" @default.
• W2840834498 type Work @default.
• W2840834498 sameAs 2840834498 @default.
• W2840834498 citedByCount "69" @default.
• W2840834498 countsByYear W28408344982018 @default.
• W2840834498 countsByYear W28408344982019 @default.
• W2840834498 countsByYear W28408344982020 @default.
• W2840834498 countsByYear W28408344982021 @default.
• W2840834498 countsByYear W28408344982022 @default.
• W2840834498 countsByYear W28408344982023 @default.
• W2840834498 crossrefType "journal-article" @default.
• W2840834498 hasAuthorship W2840834498A5012539047 @default.
• W2840834498 hasAuthorship W2840834498A5012966437 @default.
• W2840834498 hasAuthorship W2840834498A5018394997 @default.
• W2840834498 hasAuthorship W2840834498A5022178148 @default.
• W2840834498 hasAuthorship W2840834498A5025581121 @default.
• W2840834498 hasAuthorship W2840834498A5029005602 @default.
• W2840834498 hasAuthorship W2840834498A5043151851 @default.
• W2840834498 hasAuthorship W2840834498A5053041403 @default.
• W2840834498 hasAuthorship W2840834498A5056632481 @default.
• W2840834498 hasAuthorship W2840834498A5058057676 @default.
• W2840834498 hasAuthorship W2840834498A5068704522 @default.
• W2840834498 hasAuthorship W2840834498A5069895972 @default.
• W2840834498 hasAuthorship W2840834498A5073206138 @default.
• W2840834498 hasBestOaLocation W28408344981 @default.
• W2840834498 hasConcept C142724271 @default.
• W2840834498 hasConcept C180032290 @default.
• W2840834498 hasConcept C207865475 @default.
• W2840834498 hasConcept C2776070231 @default.
• W2840834498 hasConcept C2779967694 @default.
• W2840834498 hasConcept C2780381497 @default.
• W2840834498 hasConcept C2780559512 @default.
• W2840834498 hasConcept C2781244666 @default.
• W2840834498 hasConcept C502942594 @default.
• W2840834498 hasConcept C54355233 @default.
• W2840834498 hasConcept C62478195 @default.
• W2840834498 hasConcept C71924100 @default.
• W2840834498 hasConcept C81885089 @default.

• next