Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition - PubMed (original) (raw)
. 2003 May;284(5):F911-24.
doi: 10.1152/ajprenal.00183.2002. Epub 2002 Dec 27.
Affiliations
- PMID: 12505862
- DOI: 10.1152/ajprenal.00183.2002
Free article
Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition
Andras Masszi et al. Am J Physiol Renal Physiol. 2003 May.
Free article
Abstract
New research suggests that, during tubulointerstitial fibrosis, alpha-smooth muscle actin (SMA)-expressing mesenchymal cells might derive from the tubular epithelium via epithelial-mesenchymal transition (EMT). Although transforming growth factor-beta(1) (TGF-beta(1)) plays a key role in EMT, the underlying cellular mechanisms are not well understood. Here we characterized TGF-beta(1)-induced EMT in LLC-PK(1) cells and examined the role of the small GTPase Rho and its effector, Rho kinase, (ROK) in the ensuing cytoskeletal remodeling and SMA expression. TGF-beta(1) treatment caused delocalization and downregulation of cell contact proteins (ZO-1, E-cadherin, beta-catenin), cytoskeleton reorganization (stress fiber assembly, myosin light chain phosphorylation), and robust SMA synthesis. TGF-beta(1) induced a biphasic Rho activation. Stress fiber assembly was prevented by the Rho-inhibiting C3 transferase and by dominant negative (DN) ROK. The SMA promoter was activated strongly by constitutively active Rho but not ROK. Accordingly, TGF-beta(1)-induced SMA promoter activation was potently abrogated by two Rho-inhibiting constructs, C3 transferase and p190RhoGAP, but not by DN-ROK. Truncation analysis showed that the first CC(A/T)richGG (CArG B) serum response factor-binding cis element is essential for the Rho responsiveness of the SMA promoter. Thus Rho plays a dual role in TGF-beta(1)-induced EMT of renal epithelial cells. It is indispensable both for cytoskeleton remodeling and for the activation of the SMA promoter. The cytoskeletal effects are mediated via the Rho/ROK pathway, whereas the transcriptional effects are partially ROK independent.
Similar articles
- Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism.
Jeon ES, Moon HJ, Lee MJ, Song HY, Kim YM, Bae YC, Jung JS, Kim JH. Jeon ES, et al. J Cell Sci. 2006 Dec 1;119(Pt 23):4994-5005. doi: 10.1242/jcs.03281. Epub 2006 Nov 14. J Cell Sci. 2006. PMID: 17105765 - Rho activation is required for transforming growth factor-beta-induced epithelial-mesenchymal transition in lens epithelial cells.
Cho HJ, Yoo J. Cho HJ, et al. Cell Biol Int. 2007 Oct;31(10):1225-30. doi: 10.1016/j.cellbi.2007.04.006. Epub 2007 Apr 25. Cell Biol Int. 2007. PMID: 17537651 - Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition.
Park SH, Choi MJ, Song IK, Choi SY, Nam JO, Kim CD, Lee BH, Park RW, Park KM, Kim YJ, Kim IS, Kwon TH, Kim YL. Park SH, et al. J Am Soc Nephrol. 2007 May;18(5):1497-507. doi: 10.1681/ASN.2005080866. Epub 2007 Mar 27. J Am Soc Nephrol. 2007. PMID: 17389738 - Mechanisms of the epithelial-mesenchymal transition by TGF-beta.
Wendt MK, Allington TM, Schiemann WP. Wendt MK, et al. Future Oncol. 2009 Oct;5(8):1145-68. doi: 10.2217/fon.09.90. Future Oncol. 2009. PMID: 19852727 Free PMC article. Review. - TGF-beta and epithelial-to-mesenchymal transitions.
Zavadil J, Böttinger EP. Zavadil J, et al. Oncogene. 2005 Aug 29;24(37):5764-74. doi: 10.1038/sj.onc.1208927. Oncogene. 2005. PMID: 16123809 Review.
Cited by
- Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis.
Wang Y, Chen S, Bao S, Yao L, Wen Z, Xu L, Chen X, Guo S, Pang H, Zhou Y, Zhou P. Wang Y, et al. Front Immunol. 2024 Feb 15;15:1338922. doi: 10.3389/fimmu.2024.1338922. eCollection 2024. Front Immunol. 2024. PMID: 38426100 Free PMC article. Review. - Morphological and cytoskeleton changes in cells after EMT.
Nurmagambetova A, Mustyatsa V, Saidova A, Vorobjev I. Nurmagambetova A, et al. Sci Rep. 2023 Dec 13;13(1):22164. doi: 10.1038/s41598-023-48279-y. Sci Rep. 2023. PMID: 38092761 Free PMC article. - TGF-β1 signalling in Alzheimer's pathology and cytoskeletal reorganization: a specialized Tau perspective.
Kapoor M, Chinnathambi S. Kapoor M, et al. J Neuroinflammation. 2023 Mar 13;20(1):72. doi: 10.1186/s12974-023-02751-8. J Neuroinflammation. 2023. PMID: 36915196 Free PMC article. Review. - Identification of key genes associated with esophageal adenocarcinoma based on bioinformatics analysis.
Qi W, Li R, Li L, Li S, Zhang H, Tian H. Qi W, et al. Ann Transl Med. 2021 Dec;9(23):1711. doi: 10.21037/atm-21-4015. Ann Transl Med. 2021. PMID: 35071405 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous