Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle.
Publication/Presentation Date
10-31-2026
Abstract
Bladder outlet obstruction caused by benign prostatic hyperplasia in humans, as well as partial bladder outlet obstruction in animal models, is linked to reduced contractility and impaired mitochondrial function in bladder smooth muscle (BSM). However, the mechanisms underlying changes in BSM contractility and mitochondrial function are still largely unknown. Our previous study showed that increased expression of intermediate filament proteins desmin and vimentin weakens BSM contractility. In this study, we hypothesize that BSM contractile dysfunction, driven by elevated levels of desmin and vimentin, is associated with impaired mitochondrial function. Human BSM cells and murine BSM tissue with elevated levels of desmin and vimentin produce less force than control BSM. Notably, increased expression of desmin and vimentin in human BSM cells reduces mitochondrial elongation and branching, with associated decreases in the fusion proteins MFN1 and MFN2, oxygen consumption rate, and ATP levels, and an increase in mitochondrial reactive oxygen species. Microarray analysis revealed significant induction of G0/G1 switch gene 2 (G0S2) mRNA expression in desmin- and vimentin-overexpressing human BSM cells. G0S2 protein interacts with mitochondrial channel protein VDAC in desmin- and vimentin-overexpressing human BSM cells. Silencing G0S2 expression restored BSM contraction, MLC20 phosphorylation, and ATP levels, whereas reducing the mitochondrial ROS and phospho-JNK levels in human BSM cells and murine BSM tissue overexpressing desmin and vimentin. Overall, these findings show that G0S2 plays a critical role in desmin- or vimentin-mediated attenuation of BSM contraction and mitochondrial dysfunction.
Volume
40
Issue
20
First Page
72380
Last Page
72380
ISSN
1530-6860
Published In/Presented At
Javed, E., Thangavel, C., Thangavel, K., Hypolite, J., Gamache, I., Wang, Y., Addya, S., Mak, D., Syed, F., Mishra, J., Desai, V., Das, P., Villalba, D. R., Bhushan, A., Sheu, S. S., Shoyele, S. A., Seifert, E. L., Teodoro, J. G., An, S. S., Penn, R. B., … Boopathi, E. (2026). Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 40(20), e72380. https://doi.org/10.1096/fj.202502912R
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
42905320
Department(s)
Administration and Leadership
Document Type
Article