{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T20:31:52Z","timestamp":1794083512923,"version":"4.8.0"},"reference-count":26,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873996"],"award-info":[{"award-number":["81873996"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017684","name":"Foundation Research Project of Jiangsu Province","doi-asserted-by":"publisher","award":["SB2199202203"],"award-info":[{"award-number":["SB2199202203"]}],"id":[{"id":"10.13039\/501100017684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ischemia\u2013reperfusion (IR) injury induces a pro\u2010inflammatory cascade that disrupts inflammation resolution and exacerbates skeletal muscle fibrosis, leading to impaired regeneration through fibrosis and compromised myofiber regeneration. This study aimed to: (1) Demonstrate IR\u2010induced dysregulation of muscle regeneration following acute injury; (2) Elucidating how TGF\u2010\u03b21 signaling within the FAP\u2010associated inflammatory niche mediates fibrosis and impairs myofiber repair; and (3) Evaluating anti\u2010TGF\u2010\u03b2 neutralization as a mechanism\u2010based strategy to preserve regenerative capacity. Male C57BL6 mice (8\u2009weeks) received CTX injections into the tibialis anterior (TA) to induce skeletal muscle injury. Transient clamping of femoral artery and vein was induced at 3\u2009days post\u2010injury to induce IR. Mice were stratified into CTX group and CTX\u2010IR group depending on the induction of IR injury. TGF\u2010\u03b2 neutralizing antibody (TGF\u2010\u03b2 NAb) was administered in\u00a0vivo to evaluate therapeutic potential. HE and Sirius red staining was used to assess cross\u2010sectional area (CSA) of myofibers and percentage of fibrotic tissue. Western blotting was used to assess the expression of Collagen I, Collagen III and TGF\u2010\u03b2. Flow cytometry was used to assess the number of fibro\u2010adipogenic progenitors (FAPs). Collagen I and CD90 were assessed using immunostaining of TA cryosections and FAPs isolated from muscle tissues. The result shows that CTX\u2010IR mice showed smaller myofiber cross\u2010sectional area and more fibrotic tissue than CTX mice. Western blots revealed higher levels of Collagen I, Collagen III and TGF\u2010\u03b21 in CTX\u2010IR samples. TGF\u2010\u03b21 stimulated the expression of collagen I in FAPs. TGF\u2010\u03b2 NAb application ameliorated the fibrosis of skeletal muscle and improved myofiber regeneration after IR. In conclusion, IR impairs muscle regeneration through TGF\u2010\u03b2\u2010associated FAP activation and collagen deposition. Inhibition of TGF\u2010\u03b2 attenuates fibrosis and increases the CSA of myofibers, demonstrating it as a potential target for promoting structural recovery and regenerative architecture in co\u2010existing muscle injuries during orthopedic trauma.<\/jats:p>","DOI":"10.1096\/fj.202601893r","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:08Z","timestamp":1786978148000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 to Attenuate Ischemia\u2013Reperfusion Associated Muscle Fibrosis and Enhance Regeneration: A Preclinical Study"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0083-1894","authenticated-orcid":false,"given":"Hongru","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjia","family":"Zhong","sequence":"additional","affiliation":[{"name":"Laboratory For Myology, Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences Vrije University Amsterdam, Amsterdam Movement Science  Amsterdam the Netherlands"},{"name":"The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital  Qingyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital  Qingyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benlong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zezhang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00469-8"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546505274714"},{"key":"e_1_2_14_4_1","first-page":"1801","article-title":"Long\u2010Term Persistence of Disability Following Severe Lower\u2010Limb Trauma. 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