{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:16:06Z","timestamp":1788354966769,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020912","name":"King Faisal University","doi-asserted-by":"publisher","award":["KFU264728"],"award-info":[{"award-number":["KFU264728"]}],"id":[{"id":"10.13039\/501100020912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Fibroblasts are essential for tissue repair, but persistent activation of matrix\u2010remodelling myofibroblasts can promote fibrosis, tissue stiffening and immune dysfunction. LRRC15 is a leucine\u2010rich repeat\u2010containing cell\u2010surface protein enriched in selected activated mesenchymal compartments, with the strongest functional evidence arising from cancer\u2010associated stroma. State\u2010level evidence also links LRRC15 to a TGF\u2010\u03b2\u2010regulated extracellular matrix\u2010remodelling myofibroblast state in idiopathic pulmonary fibrosis and to disease\u2010specific myofibroblast programs in human skin, including inflamed hidradenitis suppurativa associated with scarring risk. However, LRRC15\u2010specific causal evidence in physiological wound repair and pathological scarring remains limited. This review therefore considers LRRC15 positivity a context\u2010dependent stromal state rather than a universal fibroblast lineage or intrinsically pathological identity. Focusing on pulmonary fibrosis and tumour stroma, with skin repair as a comparative framework, we integrate single\u2010cell transcriptomics, spatial mapping, matrix biology and cancer immunology. Current evidence supports LRRC15 as a marker of activated stromal programs and, in selected tumour models, as a contributor to immunoregulatory stromal function, but does not establish universal control of fibroblast contractility, matrix persistence, or scar formation. We propose that temporal persistence and anatomical context may distinguish adaptive from maladaptive LRRC15\u2010associated remodelling. Across tissues, these observations suggest related or convergent programs rather than a demonstrated conserved molecular identity. The proposed repair\u2010to\u2010pathology spectrum is therefore hypothesis\u2010generating and requires validation through temporal lineage tracing, tissue\u2010relevant LRRC15 perturbation, spatial protein analysis, and stage\u2010specific therapeutic studies. LRRC15 is best viewed as a biological readout and potential targeting handle whose significance must be defined in each tissue context.<\/jats:p>","DOI":"10.1111\/wrr.70206","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:26:54Z","timestamp":1788352014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>LRRC15<\/scp>\n                    + Myofibroblasts as a Stromal State Linking Repair, Fibrosis, and Scarring"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-4470","authenticated-orcid":false,"given":"Rabab S.","family":"Hamad","sequence":"first","affiliation":[{"name":"Biological Sciences Department, College of Science King Faisal University  Al Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6165-3847","authenticated-orcid":false,"given":"Elsayed A.","family":"Elmorsy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy Qassim University  Buraidah Saudi Arabia"},{"name":"Department of Clinical Pharmacology, Faculty of Medicine Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5060-0790","authenticated-orcid":false,"given":"Attalla F.","family":"El\u2010kott","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science King Khalid University  Abha Saudi Arabia"},{"name":"Department of Zoology, Faculty of Science Damanhour University  Damanhour Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"AlShehri","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Negm","sequence":"additional","affiliation":[{"name":"Health Specialties, Basic Sciences and Their Applications Unit, Applied College, Mahayil Asir King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Eltantawy","sequence":"additional","affiliation":[{"name":"Department of Biology, Program of Preparatory Year Batterjee Medical college  Aseer Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-0262","authenticated-orcid":false,"given":"Mohamed A. M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-7836","authenticated-orcid":false,"given":"Anis Ahmad","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-7851","authenticated-orcid":false,"given":"Sameh","family":"Saber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Delta University for Science and Technology  Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_22_2_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-pathol-020712-163930","article-title":"Host Responses in Tissue Repair and Fibrosis","volume":"8","author":"Duffield J. 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Molecular Cell Biology"},{"key":"e_1_2_22_30_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaa2151","article-title":"Skin Fibrosis: Identification and Isolation of a Dermal Lineage With Intrinsic Fibrogenic Potential","volume":"348","author":"Rinkevich Y.","year":"2015","journal-title":"Science"},{"issue":"11","key":"e_1_2_22_31_1","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1093\/neuonc\/noaf157","article-title":"CAF\u2010Derived LRRC15 Orchestrates Macrophage Polarization and Limits PD\u20101 Immunotherapy Efficacy in Glioblastoma","volume":"27","author":"Luo F.","year":"2025","journal-title":"Neuro\u2010Oncology"},{"issue":"10","key":"e_1_2_22_32_1","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1158\/0008-5472.CAN-25-2871","article-title":"Targeting LRRC15 in Cancer\u2010Associated Fibroblasts Modifies the Extracellular Matrix and Enhances Tumor Immune Responses to Suppress Lung Cancer Progression","volume":"86","author":"Qi L.","year":"2026","journal-title":"Cancer Research"},{"issue":"10","key":"e_1_2_22_33_1","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1016\/j.ccell.2024.08.020","article-title":"Cross\u2010Tissue Human Fibroblast Atlas Reveals Myofibroblast Subtypes With Distinct Roles in Immune Modulation","volume":"42","author":"Gao Y.","year":"2024","journal-title":"Cancer Cell"},{"key":"e_1_2_22_34_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","article-title":"A Framework for Advancing Our Understanding of Cancer\u2010Associated Fibroblasts","volume":"20","author":"Sahai E.","year":"2020","journal-title":"Nature Reviews Cancer"},{"key":"e_1_2_22_35_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/path.4104","article-title":"The Myofibroblast Matrix: Implications for Tissue Repair and Fibrosis","volume":"229","author":"Klingberg F.","year":"2013","journal-title":"Journal of Pathology"},{"issue":"6","key":"e_1_2_22_36_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.ccr.2014.04.005","article-title":"Depletion of Carcinoma\u2010Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer With Reduced Survival","volume":"25","author":"\u00d6zdemir B. 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V. 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