ArticleAmerican journal of physiology. Renal physiology2008
TGFbeta-induced RhoA activation and fibronectin production in mesangial cells require caveolae.
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- miR-299a-5p is a mediator of fibrosis in diabetic kidney disease by regulating follistatin and cripto-1.Communications biology · 2025Article
- Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis.eLife · 2024Article
- Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.Circulation research · 2023Article
- GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy.Acta pharmacologica Sinica · 2023Article
- The cellular microenvironment and cytoskeletal actin dynamics in liver fibrogenesis.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2022Article
- A Role of Caveolae in Trabecular Meshwork Mechanosensing and Contractile Tone.Frontiers in cell and developmental biology · 2022Article
- Activin A and Cell-Surface GRP78 Are Novel Targetable RhoA Activators for Diabetic Kidney Disease.International journal of molecular sciences · 2021Article
- miR299a-5p promotes renal fibrosis by suppressing the antifibrotic actions of follistatin.Scientific reports · 2021Article
- Article
- Protein Kinase A Inhibitor H89 Attenuates Experimental Proliferative Vitreoretinopathy.Investigative ophthalmology & visual science · 2020Article
- Role of Caveolin-1 in Diabetes and Its Complications.Oxidative medicine and cellular longevity · 2020Review
- Article
- Caveolin-1 regulation of Sp1 controls production of the antifibrotic protein follistatin in kidney mesangial cells.Cell communication and signaling : CCS · 2019Article
- TGF-β-induced IOP elevations are mediated by RhoA in the early but not the late fibrotic phase of open angle glaucoma.Molecular vision · 2018Article
- Signaling Mechanisms of Myofibroblastic Activation: Outside-in and Inside-Out.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018Review
- Reactive oxygen species modulator 1 regulates oxidative stress and induces renal and pulmonary fibrosis in a unilateral ureteral obstruction rat model and in HK‑2 cells.Molecular medicine reports · 2017Article
- Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy.International journal of molecular sciences · 2017Article
- Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?American journal of respiratory cell and molecular biology · 2017Review
- Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?Current diabetes reports · 2017Review
- The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is regulated by TGF-β2.Journal of cell science · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glomerular sclerosis of diverse etiologies is characterized by mesangial matrix accumulation, with transforming growth factor-beta (TGFbeta) an important pathogenic factor. The GTPase RhoA mediates TGFbeta-induced matrix accumulation in some settings. Here we study the role of the membrane microdomain caveolae in TGFbeta-induced RhoA activation and fibronectin upregulation in mesangial cells (MC). In primary rat MC, TGFbeta1 time dependently increased RhoA and downstream Rho kinase activation. Rho pathway inhibition blocked TGFbeta1-induced upregulation of fibronectin transcript and protein. TGFbeta1-induced RhoA activation was prevented by disrupting caveolae with cholesterol depletion and rescued by cholesterol repletion. Compared with wild types, RhoA/Rho kinase activation was absent in MC lacking caveolae. Reexpression of caveolin-1 (and caveolae) restored these responses. Phosphorylation of caveolin-1 on Y14, effected by Src kinases, has been implicated in signaling responses. Overexpression of nonphosphorylatable caveolin-1 Y14A prevented TGFbeta1-induced RhoA activation. TGFbeta1 also activated Src, and its inhibition blocked RhoA activation. Furthermore, TGFbeta1 led to association of RhoA and caveolin-1. This was prevented by Src or TGFbeta receptor I inhibition, and by caveolin-1 Y14A overexpression. Last, fibronectin upregulation by TGFbeta1 was blocked by Src inhibition, not seen in caveolin-1 knockout MC, and restored by caveolin-1 reexpression in the latter. TGFbeta1-induced collagen I accumulation also required caveolae. TGFbeta1-mediated Smad2/3 activation, however, did not require caveolae. We conclude that RhoA/Rho kinase mediates TGFbeta-induced fibronectin upregulation. This requires caveolae and caveolin-1 interaction with RhoA. Interference with caveolin/caveolae or RhoA signaling thus represents a potential target for the treatment of fibrotic renal disease.
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