Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2

Javed, Elham; Thangavel, Chellappagounder; Frara, Nagat; Singh, Jagmohan; Mohanty, Ipsita; Hypolite, Joseph A.; Birbe, Ruth; Braverman, Alan S.; Den, Robert B.; Rattan, Satish; Zderic, Stephen A.; Deshpande, Deepak A.; Penn, Raymond B.; Ruggieri, Michael R.; Chacko, Samuel; Boopathi, Ettickan

doi:10.1096/fj.201901301r

Cited by 5 publications

(5 citation statements)

References 68 publications

(161 reference statements)

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“…In addition, unlike the time-dependent increase in MLC phosphorylation observed in SS2-infected STECs, SS2 infection had no effect on MLC phosphorylation levels in VIM KO STECs. Our results support the idea that vimentin is associated with signal transduction [ 46 – 48 ] and further show that the Atl-vimentin interaction is required for the phosphorylation of MLC. Further work will be required to elucidate the precise mechanisms by which vimentin affects MLC phosphorylation.…”

Section: Discussionsupporting

confidence: 90%

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin

Meng

Wang

et al. 2022

PLoS Pathog

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Streptococcus suis serotype 2 (SS2) is a major zoonotic pathogen resulting in manifestations as pneumonia and septic shock. The upper respiratory tract is typically thought to be the main colonization and entry site of SS2 in pigs, but the mechanism through which it penetrates the respiratory barrier is still unclear. In this study, a mutant with low invasive potential to swine tracheal epithelial cells (STECs) was screened from the TnYLB-1 transposon insertion mutant library of SS2, and the interrupted gene was identified as autolysin (atl). Compared to wild-type (WT) SS2, Δatl mutant exhibited lower ability to penetrate the tracheal epithelial barrier in a mouse model. Purified Atl also enhanced SS2 translocation across STEC monolayers in Transwell inserts. Furthermore, Atl redistributed the tight junctions (TJs) in STECs through myosin light chain kinase (MLCK) signaling, which led to increased barrier permeability. Using mass spectrometry, co-immunoprecipitation (co-IP), pull-down, bacterial two-hybrid and saturation binding experiments, we showed that Atl binds directly to vimentin. CRISPR/Cas9-targeted deletion of vimentin in STECs (VIM KO STECs) abrogated the capacity of SS2 to translocate across the monolayers, SS2-induced phosphorylation of myosin II regulatory light chain (MLC) and MLCK transcription, indicating that vimentin is indispensable for MLCK activation. Consistently, vimentin null mice were protected from SS2 infection and exhibited reduced tracheal and lung injury. Thus, MLCK-mediated epithelial barrier opening caused by the Atl-vimentin interaction is found to be likely the key mechanism by which SS2 penetrates the tracheal epithelium.

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Section: Discussionsupporting

confidence: 90%

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin

Meng

Wang

et al. 2022

PLoS Pathog

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“…Considering that the main function of veins is not contractility, that arms veins specifically have a negligible myogenic tone [ 84 ], and that contractile proteins also play crucial functions in cell migration [ 85 ], this “contractile” phenotype in veins calls for future investigations. Along these lines, the value of desmin as a contractile marker in bladder SMCs has been recently debated [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis

Rojas,

Zigmond,

Pereira-Simon

et al. 2024

PLoS ONE

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The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking.

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“…To characterize smooth muscle phenotype, the expression of Vimentin and Smoothelin was assessed (Table 3), using immunofluorescence. [79][80][81][82][83][84] Statistical Analysis: Statistical analysis was performed on GraphPad Prism 9.4.1 (GraphPad Software, San Diego, CA; www.graphpad.com). All reported values were means ± SEM, resulting from 3-8 biological replicates.…”

Section: Methodsmentioning

confidence: 99%

“…To characterize smooth muscle phenotype, the expression of Vimentin and Smoothelin was assessed (Table 3), using immunofluorescence. [ 79–84 ]…”

Section: Methodsmentioning

confidence: 99%

Acute Exposure to Pyridostigmine Bromide Disrupts Cholinergic Myenteric Neuroimmune Function in Mice

et al. 2023

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Gulf War Illness (GWI) results from chemical exposure during the Gulf War, with notable impacts on gastrointestinal motility. Due to the limited demographic impacted by this ailment, an in‐depth investigation of the GWI has yielded little regarding the underlying pathophysiological mechanisms. Here, the hypothesis that exposure to pyridostigmine bromide (PB) results in severe enteric neuro‐inflammation, that cascades to disruptions in colonic motility, is tested. The analyses are performed on male C57BL/6 mice that are treated with physiologically similar doses of PB given to GW veterans. When colonic motility is assessed, GWI colons have significantly reduced forces in response to acetylcholine or electrical field stimulation. GWI is also accompanied by high levels of pro‐inflammatory cytokines and chemokines, associated with increased numbers of CD40+ pro‐inflammatory macrophages within the myenteric plexus. Enteric neurons responsible for mediating colonic motility reside within the myenteric plexus, and PB exposure reduced their numbers. Significant smooth muscle hypertrophy is also observed due to increased inflammation. Together, the results show that PB exposure caused functional and anatomical dysfunction, promoting impaired motility within the colon. Achieving a greater understanding of the mechanisms of GWI will allow more refinement in therapeutic options that improve veterans’ quality of life.

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Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2

Cited by 5 publications

References 68 publications

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin

Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis

Acute Exposure to Pyridostigmine Bromide Disrupts Cholinergic Myenteric Neuroimmune Function in Mice

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