ArticleJournal of cell science2013
TGFβ receptor I transactivation mediates stretch-induced Pak1 activation and CTGF upregulation in mesangial cells.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Stevioside promotes hepatocyte proliferation via YAP signaling in cholestatic disease.Acta pharmacologica Sinica · 2026Article
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- Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells.Scientific reports · 2022Article
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner.Cellular immunology · 2020Article
- The p21-activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration.British journal of pharmacology · 2018Review
- The orphan GPR50 receptor promotes constitutive TGFβ receptor signaling and protects against cancer development.Nature communications · 2018Article
- β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.Investigative ophthalmology & visual science · 2017Article
- Article
- Actin-mediated gene expression depends on RhoA and Rac1 signaling in proximal tubular epithelial cells.PloS one · 2015Article
- CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways.PloS one · 2014Article
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Increased intraglomerular pressure is an important pathogenic determinant of kidney fibrosis in the progression of chronic kidney disease, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical stretch. MC produce extracellular matrix and profibrotic cytokines, including connective tissue growth factor (CTGF) when stretched. We show that p21-activated kinase 1 (Pak1) is activated by stretch in MC in culture and in vivo in a process marked by elevated intraglomerular pressures. Its activation is essential for CTGF upregulation. Rac1 is an upstream regulator of Pak1 activation. Stretch induces transactivation of the type I transforming growth factor β1 receptor (TβRI) independently of ligand binding. TβRI transactivation is required not only for Rac1/Pak1 activation, but also for activation of the canonical TGFβ signaling intermediate Smad3. We show that Smad3 activation is an essential requirement for CTGF upregulation in MC under mechanical stress. Pak1 regulates Smad3 C-terminal phosphorylation and transcriptional activation. However, a second signaling pathway, that of RhoA/Rho-kinase and downstream Erk activation, is also required for stretch-induced CTGF upregulation in MC. Importantly, this is also regulated by Pak1. Thus, Pak1 serves as a novel central mediator in the stretch-induced upregulation of CTGF in MC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.