{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:54:35Z","timestamp":1790927675797,"version":"4.1.0"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Background: Glomerular diseases are major drivers of chronic kidney disease (CKD) and end-stage renal failure worldwide. Transforming growth factor-\u03b2 (TGF-\u03b2) is a central molecular regulator that integrates inflammatory, metabolic, and extracellular matrix remodeling pathways, thereby promoting renal fibrosis. Summary: This review synthesizes current evidence regarding TGF-\u03b2 in glomerular diseases, emphasizing its context-dependent networks across distinct compartments of the renal microenvironment. Canonical SMAD signaling coordinates transcription of profibrotic genes, while non-canonical pathways (MAPK, PI3K\/AKT, and Rho GTPases) amplify inflammatory and metabolic signaling. Rather than a uniform signaling pathway, TGF-\u03b2 is shaped by disease-specific triggers, driving podocyte injury, mesangial activation, and progressive fibrotic remodeling. Despite strong experimental support, global inhibition of TGF-\u03b2 has shown limited clinical success due to its pleiotropic roles in immune regulation and tissue homeostasis. Therapeutic strategies focused on selective modulation of distinct components, including SMAD3 inhibition, microRNA-based interventions, and extracellular vesicle\u2013mediated delivery systems, show promise in attenuating profibrotic signaling while preserving physiological functions. In parallel, advances in biomarker discovery and transcriptomic profiling support biomarker-guided patient stratification and precision-based therapeutic approaches. Key Messages: TGF-\u03b2 signaling is a major regulator of fibrogenesis in glomerular diseases but exerts context-dependent effects. Selective targeting of pathogenic signaling nodes, rather than global inhibition, combined with biomarker-guided stratification, represents a more effective therapeutic strategy. Conclusion: TGF-\u03b2 remains a compelling therapeutic target in glomerular diseases, and integrating selective pathway modulation with biomarker approaches may enable successful interventions to limit fibrosis and slow CKD progression.<\/jats:p>","DOI":"10.1159\/pat\/aehag007","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:40:05Z","timestamp":1790682005000},"source":"Crossref","is-referenced-by-count":0,"title":["Transforming Growth Factor-\u00df Signaling in Glomerular Diseases: Mechanisms of Fibrosis and Therapeutic Perspectives"],"prefix":"10.1159","author":[{"given":"Karen Martins","family":"Mendes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Obata","family":"Trevisan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Laura Carvalho","family":"Da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2084-4203","authenticated-orcid":false,"given":"Gl\u00e1ucia Eloisa Munhoz de Lion","family":"Siervo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene Ant\u00f4nia dos","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regia Caroline Peixoto","family":"Lira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Reis","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,9,30]]},"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/pat\/aehag007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:18:24Z","timestamp":1790925504000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/pat\/aehag007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/pat\/aehag007","archive":["Portico"],"relation":{},"ISSN":["1015-2008","1423-0291"],"issn-type":[{"value":"1015-2008","type":"print"},{"value":"1423-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}