{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:08:33Z","timestamp":1790780913047,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hypertrophic scar (HS), a fibroproliferative disorder of the skin with some tumor\u2010like properties, is closely related to dysregulated inflammation. PD\u20101\/PD\u2010L1 inhibitor is a promising medication for cancer therapy as its potent functions on adaptive immune response; whether it could be a candidate for HS therapy has aroused our interest. This study aimed to explore the effect and the mechanism of BMS\u2010202, a PD\u20101\/PD\u2010L1 inhibitor, in HS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten HS and adjacent normal skin tissues collected from HS patients were used to detect \u03b1\u2010SMA, collagen I, and PD\u2010L1 expression by Quantitative reverse transcription\u2010polymerase chain reaction and western blot (WB) analysis. Fibroblasts derived from HS tissues (HFBs) were exposed to diverse concentrations of BMS\u2010202, of which proliferation, migration, apoptosis, and collagen synthesis were evaluated by Cell Counting Kit\u20108, wound healing, terminal deoxynucleotidyl transferase (TdT) dUTP Nick\u2010End labeling, and [<jats:sup>3<\/jats:sup>H]\u2011proline incorporation assays, respectively. The effect of BMS\u2010202 on \u03b1\u2010SMA and collagen I expression, and transforming growth factor beta 1 (TGF\u03b21)\/Smad signaling in HFBs was also determined by WB and enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression level of PD\u2010L1 was significantly elevated in both HS tissues and HFBs, which was positively correlated with \u03b1\u2010SMA and collagen I expressions. BMS\u2010202 exerted a significant suppression effect on the cell proliferation, migration, collagen synthesis, and \u03b1\u2010SMA and collagen I expression of HFBs in a concentration\u2010dependent way; but did not affect apoptosis. Finally, BMS\u2010202 could reduce the phosphorylation of ERK1\/2, Smad2, and Smad3, and the TGF\u03b21 expression once its concentration reached 2.5\u2009nM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BMS\u2010202 effectively suppressed proliferation, migration, and extracellular matrix deposition of HFBs, potentially through the regulation of the ERK and TGF\u03b21\/Smad signaling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.693","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T07:24:01Z","timestamp":1662535441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["BMS\u2010202, a PD\u20101\/PD\u2010L1 inhibitor, decelerates the pro\u2011fibrotic effects of fibroblasts derived from scar tissues via ERK and TGF\u03b21\/Smad signaling 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