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The expression of CSRP2 encoding the LIM domain protein CRP2 is mediated by TGF-beta in smooth muscle and hepatic stellate cells.
Biochem Biophys Res Commun. 2006 Jul 14; 345(4):1526-35.BB

Abstract

Transforming growth factor-beta (TGF-beta) is a cytokine implicated in differentiation of smooth muscle cells and other mesenchymal-derived cells. During hepatic fibrogenesis, TGF-beta has a pivotal role in the initiation, promotion, and progression of transdifferentiation of hepatic stellate cells into myofibroblasts that play a central role in the synthesis of extracellular matrix components. Both, smooth muscle and activated hepatic stellate cells, express smooth muscle alpha-actin, the calponin-related protein SM22alpha, and CSRP2 encoding the cysteine- and glycine-rich LIM domain protein 2 (CRP2). The aim of the present study was to determine whether the expression of CSRP2 is influenced by TGF-beta. Stimulation as well as sequestering experiments demonstrated that TGF-beta markedly influences CSRP2 gene activity. Inhibition experiments using the ALK5 inhibitor SB-431542 further reveal that the transcriptional stimulation of the CSRP2 gene is mediated via the ALK5/Smad2/Smad3 signalling pathway. By use of bisulfite genomic analysis of CpG islands within the 5' regulatory regions we could exclude methylation-associated silencing, previously found to be responsible for the transcriptional inactivity of CSRP2 in a variety of human cancer cells and in a multistage carcinogenesis model, as a cause for CSRP2 inactivity in hepatocytes or fully transdifferentiated myofibroblasts.

Authors+Show Affiliations

Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16735029

Citation

Herrmann, Jens, et al. "The Expression of CSRP2 Encoding the LIM Domain Protein CRP2 Is Mediated By TGF-beta in Smooth Muscle and Hepatic Stellate Cells." Biochemical and Biophysical Research Communications, vol. 345, no. 4, 2006, pp. 1526-35.
Herrmann J, Borkham-Kamphorst E, Haas U, et al. The expression of CSRP2 encoding the LIM domain protein CRP2 is mediated by TGF-beta in smooth muscle and hepatic stellate cells. Biochem Biophys Res Commun. 2006;345(4):1526-35.
Herrmann, J., Borkham-Kamphorst, E., Haas, U., Van de Leur, E., Fraga, M. F., Esteller, M., Gressner, A. M., & Weiskirchen, R. (2006). The expression of CSRP2 encoding the LIM domain protein CRP2 is mediated by TGF-beta in smooth muscle and hepatic stellate cells. Biochemical and Biophysical Research Communications, 345(4), 1526-35.
Herrmann J, et al. The Expression of CSRP2 Encoding the LIM Domain Protein CRP2 Is Mediated By TGF-beta in Smooth Muscle and Hepatic Stellate Cells. Biochem Biophys Res Commun. 2006 Jul 14;345(4):1526-35. PubMed PMID: 16735029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The expression of CSRP2 encoding the LIM domain protein CRP2 is mediated by TGF-beta in smooth muscle and hepatic stellate cells. AU - Herrmann,Jens, AU - Borkham-Kamphorst,Erawan, AU - Haas,Ute, AU - Van de Leur,Eddy, AU - Fraga,Mario F, AU - Esteller,Manel, AU - Gressner,Axel M, AU - Weiskirchen,Ralf, Y1 - 2006/05/22/ PY - 2006/05/06/received PY - 2006/05/10/accepted PY - 2006/6/1/pubmed PY - 2006/8/17/medline PY - 2006/6/1/entrez SP - 1526 EP - 35 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 345 IS - 4 N2 - Transforming growth factor-beta (TGF-beta) is a cytokine implicated in differentiation of smooth muscle cells and other mesenchymal-derived cells. During hepatic fibrogenesis, TGF-beta has a pivotal role in the initiation, promotion, and progression of transdifferentiation of hepatic stellate cells into myofibroblasts that play a central role in the synthesis of extracellular matrix components. Both, smooth muscle and activated hepatic stellate cells, express smooth muscle alpha-actin, the calponin-related protein SM22alpha, and CSRP2 encoding the cysteine- and glycine-rich LIM domain protein 2 (CRP2). The aim of the present study was to determine whether the expression of CSRP2 is influenced by TGF-beta. Stimulation as well as sequestering experiments demonstrated that TGF-beta markedly influences CSRP2 gene activity. Inhibition experiments using the ALK5 inhibitor SB-431542 further reveal that the transcriptional stimulation of the CSRP2 gene is mediated via the ALK5/Smad2/Smad3 signalling pathway. By use of bisulfite genomic analysis of CpG islands within the 5' regulatory regions we could exclude methylation-associated silencing, previously found to be responsible for the transcriptional inactivity of CSRP2 in a variety of human cancer cells and in a multistage carcinogenesis model, as a cause for CSRP2 inactivity in hepatocytes or fully transdifferentiated myofibroblasts. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16735029/The_expression_of_CSRP2_encoding_the_LIM_domain_protein_CRP2_is_mediated_by_TGF_beta_in_smooth_muscle_and_hepatic_stellate_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)01100-4 DB - PRIME DP - Unbound Medicine ER -