Verma, P., Yalavarthi, B., Bhattacharyya, S. et al. (11 more authors) (2025) Morphological reprogramming of primary cilia length mitigates the fibrotic phenotype in fibroblasts across diverse fibrotic conditions. Journal of Cell Science. ISSN: 0021-9533
Abstract
Myofibroblast differentiation, shared across fibrotic diseases, is marked by actin polymerization and assembly of αsmooth muscle actin (αSMA) stress fibers. 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 with profibrotic TGF-β1 induced PC shortening, while silencing ACTA2 in systemic sclerosis (SSc) skin fibroblasts caused PC elongation. Importantly, we found that PC length was negatively correlated with αSMA levels in TGF-β1-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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Fibrosis, Myofibroblast, Primary cilia, Systemic sclerosis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Date Deposited: | 02 Oct 2025 15:40 |
Last Modified: | 02 Oct 2025 15:40 |
Status: | Published online |
Publisher: | The Company of Biologists |
Identification Number: | 10.1242/jcs.264191 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:232461 |