{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:29:46Z","timestamp":1794022186489,"version":"4.8.0"},"reference-count":142,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This document provides an updated overview of the molecular mechanisms underlying pulmonary fibrosis associated with Systemic Sclerosis (SSc). It summarizes current knowledge on how immune activation, vascular injury, and impaired tissue repair contribute to interstitial lung disease (ILD), which is the most serious and life-threatening complication of SSc. SSc is a rare autoimmune disorder involving vascular dysfunction and progressive fibrosis of the skin and internal organs. In the lungs, the interaction between immune and vascular abnormalities and excessive extracellular matrix deposition leads to irreversible structural damage. These processes occur through complex, multifactorial mechanisms that are only partially understood. The review examines recent evidence on the cellular mediators, signaling pathways, and epigenetic alterations involved in ILD-SSc pathogenesis. It also discusses the potential roles of genetic predisposition, environmental factors, and autoantibody profiles in disease heterogeneity. Finally, it highlights emerging therapeutic strategies that target these molecular mechanisms. This work aims to integrate these advances to provide a clearer understanding of the biological basis of SSc-associated pulmonary fibrosis and support the development of novel diagnostic and therapeutic approaches that may improve patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms262010103","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T10:28:36Z","timestamp":1760696916000},"page":"10103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Advances in the Molecular Mechanisms of Pulmonary Fibrosis in Systemic Sclerosis: A Comprehensive Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Mar\u00eda Pilar Iranzo","family":"Alcolea","sequence":"first","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0666-3035","authenticated-orcid":false,"given":"Grisell","family":"Starita Fajardo","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Pe\u00f1a Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-4460","authenticated-orcid":false,"given":"David","family":"Lucena L\u00f3pez","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5648-4057","authenticated-orcid":false,"given":"Cecilia","family":"Su\u00e1rez Caranto\u00f1a","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"L\u00f3pez Paraja","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-3684","authenticated-orcid":false,"given":"Ana","family":"Garc\u00eda de Vicente","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-2280","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Viteri-No\u00ebl","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-9523","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Gonz\u00e1lez Garc\u00eda","sequence":"additional","affiliation":[{"name":"Systemic Autoinmmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ccm.2019.05.001","article-title":"Pulmonary manifestations of systemic sclerosis and mixed connective tissue disease","volume":"40","author":"Perelas","year":"2019","journal-title":"Clin. 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