Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle.
8 affiliations
- 1Department of Medicine, Center for Translational Medicine, Philadelphia, Pennsylvania, USA.
- 2Department of Pharmaceutical Science, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
- 3Department of Biochemistry, Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, Quebec, Canada.
- 4Department of Biochemistry, McGill University, Montréal, Quebec, Canada.
- 5Cancer Genomics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
- 6Department of Pharmacology, Rutgers Institute for Translational Medicine and Science, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
- 7Cooper University Hospital, Camden, New Jersey, USA.
- 8Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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.
Related
- The Prognostic Role of Vimentin Expression in Triple‐Negative Breast Cancer: A Retrospective Cohort Study
- Cholesterol-Mediated Modulation of Collecting Lymphatic Vessel Contractility: Exploring Cholesterol Depletion as a Therapeutic Alternative to Improve Lymphatic Function in Hypercholesterolemia
- Increased expression of hPGDS‑PGD2 in patients with eosinophilic chronic rhinosinusitis with nasal polyps
- Colonic LRRK2 expression is increased in Crohn's disease but not in Parkinson's disease and idiopathic RBD
- Prostaglandin-Endoperoxide Synthase 2 (PTGS2) Expression Is Increased in Chronic Asymptomatic Orchitis in the Dog.
BibTeX
@article{javed2026increased,
title = {{Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle.}},
author = {Elham Javed and Chellappagounder Thangavel and Karthik Thangavel and Joseph Hypolite and Isabelle Gamache and Yilin Wang and Sankar Addya and Darin Mak and Furqan Syed and Jyotsna Mishra and Vilas Desai and Pragnya Das and Dominic R Villalba and Alok Bhushan and Shey-Shing Sheu and Sunday A Shoyele and Erin L Seifert and Jose G Teodoro and Steven S An and Raymond B Penn and Deepak A Deshpande and Ettickan Boopathi},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2026},
month = oct,
doi = {10.1096/fj.202502912r},
url = {https://europepmc.org/article/MED/42905320},
note = {CC BY},
}
RIS
TY - JOUR
TI - Increased Expression of Desmin and Vimentin Impairs Mitochondrial Function and Reduces Contractility via G0S2 in Bladder Smooth Muscle.
AU - Elham Javed
AU - Chellappagounder Thangavel
AU - Karthik Thangavel
AU - Joseph Hypolite
AU - Isabelle Gamache
AU - Yilin Wang
AU - Sankar Addya
AU - Darin Mak
AU - Furqan Syed
AU - Jyotsna Mishra
AU - Vilas Desai
AU - Pragnya Das
AU - Dominic R Villalba
AU - Alok Bhushan
AU - Shey-Shing Sheu
AU - Sunday A Shoyele
AU - Erin L Seifert
AU - Jose G Teodoro
AU - Steven S An
AU - Raymond B Penn
AU - Deepak A Deshpande
AU - Ettickan Boopathi
PY - 2026
DA - 2026/10/01
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DO - 10.1096/fj.202502912r
UR - https://europepmc.org/article/MED/42905320
AB - 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.
SN - 0892-6638
SN - 1530-6860
ER -