Matches in SemOpenAlex for { <https://semopenalex.org/work/W2225234075> ?p ?o ?g. }
- W2225234075 endingPage "586" @default.
- W2225234075 startingPage "575" @default.
- W2225234075 abstract "Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E2, due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE2 production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE2 production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE2 synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4." @default.
- W2225234075 created "2016-06-24" @default.
- W2225234075 creator A5008098676 @default.
- W2225234075 creator A5010568573 @default.
- W2225234075 creator A5015770154 @default.
- W2225234075 creator A5025109546 @default.
- W2225234075 creator A5026940499 @default.
- W2225234075 creator A5029636558 @default.
- W2225234075 creator A5037311694 @default.
- W2225234075 creator A5044926125 @default.
- W2225234075 creator A5050721723 @default.
- W2225234075 creator A5055114063 @default.
- W2225234075 creator A5055559154 @default.
- W2225234075 creator A5058325633 @default.
- W2225234075 date "2016-03-08" @default.
- W2225234075 modified "2023-10-03" @default.
- W2225234075 title "Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis" @default.
- W2225234075 cites W1668188286 @default.
- W2225234075 cites W1826797943 @default.
- W2225234075 cites W1831445971 @default.
- W2225234075 cites W1916902066 @default.
- W2225234075 cites W1967841068 @default.
- W2225234075 cites W1973446038 @default.
- W2225234075 cites W1973977844 @default.
- W2225234075 cites W1975511102 @default.
- W2225234075 cites W1976761827 @default.
- W2225234075 cites W1978998797 @default.
- W2225234075 cites W1980193533 @default.
- W2225234075 cites W1997495854 @default.
- W2225234075 cites W1999079520 @default.
- W2225234075 cites W2005477943 @default.
- W2225234075 cites W2010608162 @default.
- W2225234075 cites W2013414651 @default.
- W2225234075 cites W2031738318 @default.
- W2225234075 cites W2032791083 @default.
- W2225234075 cites W2041217784 @default.
- W2225234075 cites W2041426770 @default.
- W2225234075 cites W2042052097 @default.
- W2225234075 cites W2042440356 @default.
- W2225234075 cites W2073763489 @default.
- W2225234075 cites W2077654571 @default.
- W2225234075 cites W2077888205 @default.
- W2225234075 cites W2081741824 @default.
- W2225234075 cites W2088711557 @default.
- W2225234075 cites W2095947403 @default.
- W2225234075 cites W2096227701 @default.
- W2225234075 cites W2096809504 @default.
- W2225234075 cites W2098412954 @default.
- W2225234075 cites W2103966606 @default.
- W2225234075 cites W2110777286 @default.
- W2225234075 cites W2116793797 @default.
- W2225234075 cites W2130098255 @default.
- W2225234075 cites W2131813265 @default.
- W2225234075 cites W2132075254 @default.
- W2225234075 cites W2135293703 @default.
- W2225234075 cites W2140386277 @default.
- W2225234075 cites W2149072783 @default.
- W2225234075 cites W2159893642 @default.
- W2225234075 cites W2162379653 @default.
- W2225234075 cites W2163125553 @default.
- W2225234075 cites W2163999275 @default.
- W2225234075 cites W2164113977 @default.
- W2225234075 cites W2166874505 @default.
- W2225234075 doi "https://doi.org/10.1042/cs20150697" @default.
- W2225234075 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4782165" @default.
- W2225234075 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26744410" @default.
- W2225234075 hasPublicationYear "2016" @default.
- W2225234075 type Work @default.
- W2225234075 sameAs 2225234075 @default.
- W2225234075 citedByCount "60" @default.
- W2225234075 countsByYear W22252340752016 @default.
- W2225234075 countsByYear W22252340752017 @default.
- W2225234075 countsByYear W22252340752018 @default.
- W2225234075 countsByYear W22252340752019 @default.
- W2225234075 countsByYear W22252340752020 @default.
- W2225234075 countsByYear W22252340752021 @default.
- W2225234075 countsByYear W22252340752022 @default.
- W2225234075 countsByYear W22252340752023 @default.
- W2225234075 crossrefType "journal-article" @default.
- W2225234075 hasAuthorship W2225234075A5008098676 @default.
- W2225234075 hasAuthorship W2225234075A5010568573 @default.
- W2225234075 hasAuthorship W2225234075A5015770154 @default.
- W2225234075 hasAuthorship W2225234075A5025109546 @default.
- W2225234075 hasAuthorship W2225234075A5026940499 @default.
- W2225234075 hasAuthorship W2225234075A5029636558 @default.
- W2225234075 hasAuthorship W2225234075A5037311694 @default.
- W2225234075 hasAuthorship W2225234075A5044926125 @default.
- W2225234075 hasAuthorship W2225234075A5050721723 @default.
- W2225234075 hasAuthorship W2225234075A5055114063 @default.
- W2225234075 hasAuthorship W2225234075A5055559154 @default.
- W2225234075 hasAuthorship W2225234075A5058325633 @default.
- W2225234075 hasBestOaLocation W22252340751 @default.
- W2225234075 hasConcept C104317684 @default.
- W2225234075 hasConcept C142724271 @default.
- W2225234075 hasConcept C150194340 @default.
- W2225234075 hasConcept C153911025 @default.
- W2225234075 hasConcept C173396325 @default.
- W2225234075 hasConcept C190727270 @default.