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Although the anti\u2010fibrotic tetrapeptide Ac\u2010SDKP has shown promise in reducing fibrosis, the specific molecular mechanisms through which it modulates apoptosis in silica\u2010induced lung injury remain unclear, particularly the role of heat shock protein 27 (HSP27).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wistar rats were divided into groups including control, model (2\u2010week, 3\u2010week, and 4\u2010week), and Ac\u2010SDKP prevention\/treatment groups. In\u00a0vitro, MEF and A549 cells were treated with TGF\u2010\u03b21 and Ac\u2010SDKP to observe the effects on apoptosis\u2010related proteins. Additionally, HSP27 interference vectors were constructed to study its role in regulating apoptosis via FAS\/FASL and mitochondrial pathways in both in\u00a0vivo and in\u00a0vitro models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo, Ac\u2010SDKP administration alleviated silica\u2010induced pulmonary fibrosis and reduced apoptosis in lung tissue. In contrast, in\u00a0vitro, TGF\u2010\u03b21 stimulation suppressed apoptosis in A549 and MEF cells, whereas Ac\u2010SDKP restored apoptotic activity by regulating the HSP27\u2010mediated FAS\/FASL and mitochondrial pathways. Moreover, AAV9\u2010mediated knockdown of HSP27 in mice enhanced apoptosis and attenuated fibrosis, confirming the anti\u2010apoptotic role of HSP27 in silicosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reveal that Ac\u2010SDKP exerts context\u2010dependent modulation of apoptosis through HSP27\u2014protecting acutely injured alveolar epithelial cells in\u00a0vivo while reinstating apoptotic signaling in EMT\u2010adapted A549 and MEF cells in\u00a0vitro. Thus, targeting HSP27 may offer a promising therapeutic strategy to restore apoptotic\u2013fibrotic equilibrium in silicosis and related pulmonary fibrotic disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70272","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:52:04Z","timestamp":1786002724000},"page":"1928-1955","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ac\u2010\n                    <scp>SDKP<\/scp>\n                    modulates apoptosis via\n                    <scp>HSP27<\/scp>\n                    and the\n                    <scp>FAS<\/scp>\n                    \/\n                    <scp>FASL<\/scp>\n                    and mitochondrial axes"],"prefix":"10.1002","volume":"9","author":[{"given":"Wenxin","family":"Guo","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and 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