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The molecular basis for these findings, however, remains to be clarified. HSFs were subjected to TSG\u20106 treatment. Treatment with TSG\u20106 significantly suppressed HSF proliferation and induced them to undergo apoptosis. Moreover, TSG\u20106 exposure led to reductions in collagen I, collagen III, and \u03b1\u2010SMA mRNA and protein levels, with a corresponding drop in proliferating cell nuclear antigen (PCNA) expression indicative of impaired proliferative activity. Endoplasmic reticulum (ER) stress was also suppressed in these HSFs as demonstrated by decreases in Bip and p\u2010IRE1\u03b1 expression, downstream inositol requiring enzyme 1 alpha (IRE1\u03b1) \u2010Tumor necrosis factor receptor associated factor 2\u00a0(TRAF2) pathway signalling was inhibited and treated cells failed to induce NF\u2010\u03baB, TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106 expression. Overall, ER stress was found to trigger inflammatory activity in HSFs via the IRE1\u03b1\u2010TRAF2 axis, as confirmed with the specific inhibitor of IRE1\u03b1 STF083010. Additionally, the effects of TSG\u20106 on apoptosis, collagen I, collagen III, \u03b1\u2010SMA, and PCNA of HSFs were reversed by the IRE1\u03b1 activator thapsigargin (TG). These data suggest that TSG\u20106 administration can effectively suppress the proliferation of HSFs in part via the inhibition of IRE1\u03b1\u2010mediated ER stress\u2010induced inflammation (IRE1\u03b1\/TRAF2\/NF\u2010\u03baB signalling).<\/jats:p>","DOI":"10.1111\/iwj.13950","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T04:44:26Z","timestamp":1662180266000},"page":"1008-1019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>TSG<\/scp>\u20106 inhibits hypertrophic scar fibroblast proliferation by regulating <scp>IRE1\u03b1<\/scp>\/<scp>TRAF2<\/scp>\/<scp>NF\u2010\u03baB<\/scp> signalling"],"prefix":"10.1111","volume":"20","author":[{"given":"Li","family":"Ma","sequence":"first","affiliation":[{"name":"Clinical College of Integrated Traditional Chinese and Western Medicine Anhui University of Traditional Chinese Medicine  Hefei 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