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This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) production affected AT2 cell senescence, and then explored the effect of H\n                      <jats:sub>2<\/jats:sub>\n                      S on the communication between AT2 and fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      ICR mice were intratracheally administered with bleomycin (3\u2009mg\/kg). Sodium hydrosulfide (NaHS, 28\u2009\u03bcmol\/kg\/d) was intraperitoneally injected for 2\u2009weeks. The H\n                      <jats:sub>2<\/jats:sub>\n                      S\u2010generating enzyme cystathionine\u2010\u03b2\u2010synthase (CBS) knockout heterozygous (CBS\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      ) mice were used as a low H\n                      <jats:sub>2<\/jats:sub>\n                      S production model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of microarray datasets revealed downregulation of H\n                      <jats:sub>2<\/jats:sub>\n                      S\u2010generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H\n                      <jats:sub>2<\/jats:sub>\n                      S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin\u2010induced lung fibrosis. CBS\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice as compared to control mice. H\n                      <jats:sub>2<\/jats:sub>\n                      S donor NaHS attenuated bleomycin\u2010induced AT2 cell senescence both in\u00a0vivo and in\u00a0vitro. H\n                      <jats:sub>2<\/jats:sub>\n                      S donor suppressed bleomycin\u2010induced senescence\u2010associated secretory phenotype (SASP) of AT2 cells via inhibiting p53\/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H\n                      <jats:sub>2<\/jats:sub>\n                      S suppressed p53 expression by enhancing the mouse double\u2010minute 2 homologue (MDM2)\u2010mediated ubiquitination and degradation of p53.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      H\n                      <jats:sub>2<\/jats:sub>\n                      S inactivated p53\u2010p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H\n                      <jats:sub>2<\/jats:sub>\n                      S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.14059","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:08:22Z","timestamp":1700662102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hydrogen sulfide inhibits alveolar type II cell senescence and limits pulmonary fibrosis via promoting MDM2\u2010mediated p53 degradation"],"prefix":"10.1111","volume":"240","author":[{"given":"Xiu\u2010Li","family":"Wang","sequence":"first","affiliation":[{"name":"School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport  Shanghai 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