{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:27:59Z","timestamp":1786523279719,"version":"build-2736575974"},"reference-count":59,"publisher":"SAGE Publications","issue":"10-12","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82572807"],"award-info":[{"award-number":["82572807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Skin fibrosis is a hallmark of scleroderma and other fibrotic skin disorders, yet effective therapies remain limited. Immune-derived metabolites have emerged as regulators of inflammation and tissue remodeling, but whether metabolic reprogramming within dermal fibroblasts contributes to skin fibrosis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Human fibrotic skin samples, a bleomycin-induced mouse model, and primary dermal fibroblasts were used to investigate the role of immune-responsive gene 1 (\n                      <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                      ) and its metabolic product itaconate. Transcriptomic analyses, metabolic profiling, pharmacologic modulation, and genetic perturbation were employed to define downstream signaling mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Findings:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                      expression and endogenous itaconate levels were reduced in fibrotic human and murine skin. Restoration of itaconate significantly attenuated dermal thickening, collagen deposition, and fibroblast activation. Mechanistically, itaconate suppressed glycolytic reprogramming in activated fibroblasts, as evidenced by reduced glucose uptake, lactate production, and glycolytic enzyme expression. This metabolic effect was associated with inhibition of the Akt\/GSK-3\u03b2 pathway, destabilization of hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1), and subsequent downregulation of lactate dehydrogenase A (LDHA) transcription. Genetic or pharmacologic interference with HIF-1\u03b1 or LDHA partially phenocopied itaconate\u2019s antifibrotic effects, supporting a functional link between itaconate signaling, fibroblast metabolism, and fibrotic progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      This study identifies loss of Irg1-itaconate signaling as a previously unrecognized driver of fibroblast metabolic reprogramming in skin fibrosis. By revealing a fibroblast-intrinsic, metabolism-centered mechanism linking immunometabolite deficiency to extracellular matrix overproduction, these findings extend itaconate\u2019s scope beyond immune regulation and highlight metabolic targeting of fibroblasts as a promising therapeutic strategy for fibrotic skin disease.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 45, 512\u2013533.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261467594","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:07:52Z","timestamp":1784020072000},"page":"512-533","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Itaconate Ameliorates Skin Fibrosis Through Inhibition of HIF-1\u03b1\/LDHA-Driven Aerobic Glycolysis"],"prefix":"10.1177","volume":"45","author":[{"given":"Linxiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, Tongji University School of Medicine, Shanghai, China."},{"name":"Department of Orthopedics, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China."},{"name":"Department of Orthopedics, 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