ArticleAmerican journal of physiology. Renal physiology2009
Rac1 promotes TGF-beta-stimulated mesangial cell type I collagen expression through a PI3K/Akt-dependent mechanism.
Article in American journal of physiology. Renal physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- ELMO1 and Rac1 Signaling in Kidney Disease: Molecular Mechanisms, Context-Dependent Roles, and Therapeutic Potential.Biomedicines · 2026Review
- Promoting collagen synthesis: a viable strategy to combat skin ageing.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Review
- Suramin enhances chondrogenic properties by regulating the p67Bone & joint research · 2022Article
- Tauroursodeoxycholic acid inhibits TGF-β1-induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress.Experimental and therapeutic medicine · 2022Article
- DOCK-t(w)o Pleural Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- YAP mediates the interaction between the Hippo and PI3K/Akt pathways in mesangial cell proliferation in diabetic nephropathy.Acta diabetologica · 2021Article
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- The Influence of a Nanopatterned Scaffold that Mimics Abnormal Renal Mesangial Matrix on Mesangial Cell Behavior.International journal of molecular sciences · 2019Article
- sFRP1 exerts effects on gastric cancer cells through GSK3β/Rac1‑mediated restraint of TGFβ/Smad3 signaling.Oncology reports · 2019Article
- FAR2 is associated with kidney disease in mice and humans.Physiological genomics · 2018Article
- The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes.International journal of molecular sciences · 2018Article
- Transforming growth factor β: A potential biomarker and therapeutic target of ventricular remodeling.Oncotarget · 2017Review
- SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-β1 signaling.Virus research · 2017Article
- Transforming growth factor-β1/Smad3-independent epithelial-mesenchymal transition in type I collagen glomerulopathy.International journal of nephrology and renovascular disease · 2017Article
- S-Adenosylmethionine suppresses the expression of Smad3/4 in activated human hepatic stellate cells via Rac1 promoter methylation.Molecular medicine reports · 2016Article
- Anthocyanins protected hearts against ischemic injury by reducing MMP-2 activity via Akt/P38 pathways.American journal of translational research · 2016Article
- Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy.Cellular signalling · 2015Article
- AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4.BMC cell biology · 2015Article
- Hierarchy of molecules in TGF-β1 signaling relevant to myofibroblast activation and renal fibrosis.American journal of physiology. Renal physiology · 2014Article
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Authors and funding
4 authors at 3 institutions in 1 country.
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Abstract
Transforming growth factor (TGF)-beta is a central mediator in the progression of glomerulosclerosis, leading to accumulation of aberrant extracellular matrix proteins and inappropriate expression of smooth muscle alpha-actin in the kidney. Previously, we reported that disrupting the cytoskeleton diminished TGF-beta-stimulated type I collagen accumulation in human mesangial cells. As cytoskeletal signaling molecules, including the Rho-family GTPases, have been implicated in fibrogenesis, we sought to determine the respective roles of RhoA and Rac1 in HMC collagen I expression. TGF-beta1 activated both RhoA and Rac1 within 5 min of treatment, and this activation was dependent on the kinase activity of the type I TGF-beta receptor. TGF-beta1-stimulated induction of type I collagen mRNA expression and promoter activity was diminished by inhibiting Rac1 activity and was increased by a constitutively active Rac1 mutant, whereas inhibiting RhoA activity had no such effect. Rac1 activation required phosphatidylinositol-3-kinase (PI3K) activity. Furthermore, the PI3K antagonist, LY294002, reduced TGF-beta1-stimulated COL1A2 promoter activity and Rac1 activation. It also partially blocked active Rac1-stimulated collagen promoter activity, suggesting that PI3K activity contributes to both TGF-beta activation of Rac1 and signal propagation downstream of Rac1. Thus, while both Rac1 and RhoA are rapidly activated in response to TGF-beta1 in human mesangial cells, only Rac1 activation enhances events that contribute to mesangial cell collagen expression, through a positive feedback loop involving PI3K.
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