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Primary cilia (PC) are solitary membrane-bound organelles present on the majority of cells. PC length regulation is a complex process influenced by actin polymerization. We discovered that fibroblasts from diverse fibrotic conditions display significantly reduced PC length ex vivo. Treatment of healthy fibroblasts (non-fibrotic) with profibrotic TGF-\u03b21 induced PC shortening, whereas silencing ACTA2 in systemic sclerosis (SSc) skin fibroblasts caused PC elongation. Importantly, we found that PC length was negatively correlated with \u03b1SMA levels in TGF-\u03b21-treated healthy fibroblasts and pharmacologically dedifferentiated myofibroblasts. Our results suggest that during the fibrotic response, higher-order actin polymerization, along with microtubule destabilization by tubulin deacetylation, drives PC length shortening. In contrast, PC length elongation via stabilization of microtubule polymerization mitigates the fibrotic phenotype in fibrotic fibroblasts. These results reveal a potential link between PC length and fibroblast activation conserved across multiple fibrotic conditions. Our observations suggest that modulation of PC length might represent a novel therapeutic strategy for SSc and other treatment-resistant diseases associated with fibrosis.<\/jats:p>","DOI":"10.1242\/jcs.264191","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T07:51:07Z","timestamp":1758095467000},"source":"Crossref","is-referenced-by-count":9,"title":["Morphological reprogramming of primary cilia length mitigates the fibrotic phenotype in fibroblasts across diverse fibrotic conditions"],"prefix":"10.1242","volume":"138","author":[{"given":"Priyanka","family":"Verma","sequence":"first","affiliation":[{"name":"University of Michigan 1 Department of Internal Medicine , , Ann Arbor, MI 48109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Yalavarthi","sequence":"additional","affiliation":[{"name":"University of Michigan 1 Department of Internal Medicine , , Ann Arbor, MI 48109 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