{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:56:53Z","timestamp":1776056213167,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Regulatory T (Treg) cells play crucial roles in myocardial fibrosis, a key pathological feature of diabetic cardiomyopathy (DCM). Deleted in breast cancer 1 (DBC1) has emerged as an inhibitor of the immunosuppressive function of Treg cells in inflammatory states. Here, we studied the subpopulation differentiation and function of Treg cells in the myocardium of DCM and explored the role of DBC1 in Treg cell differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      DBC1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      , DBC1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      -Fxop3\n                      <jats:sup>Cre<\/jats:sup>\n                      , HIF-1\u03b1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      -Fxop3\n                      <jats:sup>Cre<\/jats:sup>\n                      , PPAR-\u03b3\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      -Fxop3\n                      <jats:sup>Cre<\/jats:sup>\n                      DCM mouse models were established to evaluate the effects of DBC, HIF-1\u03b1, and PPAR-\u03b3 on cardiac fibrosis and function. Adoptive transfer therapy was performed to assess the impact of ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Areg\n                      <jats:sup>hi<\/jats:sup>\n                      Treg cells. Flow cytometry was used to confirm the role of DBC1 in Treg cell differentiation. Co-culture systems were performed to analyze the effect of ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Areg\n                      <jats:sup>hi<\/jats:sup>\n                      Treg cells on fibroblast behaviors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ST2\n                      <jats:sup>+<\/jats:sup>\n                      Treg subsets were increased in the hearts of DCM mice and exhibited increased Areg expression. DBC1 was upregulated in DCM mice and promoted myocardial fibrosis. ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Areg\n                      <jats:sup>hi<\/jats:sup>\n                      Treg subsets exhibited increased DBC1 expression and promoted myocardial fibrosis by producing Areg. ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Treg subsets promoted the viability, migration, and fibrosis of mouse CFs through Areg paracrine secretion\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Furthermore, DBC1 enhanced the differentiation of myocardial Treg cells into the ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Areg\n                      <jats:sup>hi<\/jats:sup>\n                      subgroup in DCM through the HIF-1\u03b1-PPAR-\u03b3 axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our current investigation shows that the DBC1-HIF-1\u03b1-PPAR-\u03b3 axis promotes the differentiation of myocardial Treg cells into the ST2\n                      <jats:sup>hi<\/jats:sup>\n                      Areg\n                      <jats:sup>hi<\/jats:sup>\n                      pro-fibrotic subgroup, which drives maladaptive myocardial fibrosis and cardiac dysfunction via paracrine secretion of Areg in DCM mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1780666","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:39:41Z","timestamp":1776055181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The DBC1-HIF-1\u03b1-PPAR-\u03b3 axis regulates Treg cell differentiation to promote myocardial fibrosis in experimental diabetic cardiomyopathy through the paracrine secretion of Areg"],"prefix":"10.3389","volume":"17","author":[{"given":"Linhe","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University","place":["Xi\u2019an, China"]},{"name":"Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University","place":["Xi\u2019an, 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