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Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in vitro.
Life Sci. 2004 Jun 04; 75(3):367-79.LS

Abstract

Connective tissue growth factor (CTGF) has been reported to play an important role in mediating the profibrotic effects of transforming growth factor-beta (TGF-beta) in the pathogenesis of renal fibrosis. To further elucidate the role of CTGF in renal tubular transdifferentiation and extracellular matrix (ECM) metabolism, we examined the time-course of CTGF, alpha-smooth muscle actin (alpha-SMA), fibronectin and plasminogen activator inhibitor-1(PAI-1) gene expression upon the stimulation of TGF-beta1 (5 microg/L) in cultured human proximal tubular epithelial cell line (HKC), and further investigated the effects of endogenous CTGF blockade. On reverse transcriptional-polymerase chain reaction (RT-PCR) analysis, TGF-beta1 upregulated CTGF gene expression, preceding that of alpha-SMA, fibronectin and PAI-1. The alpha-SMA, fibronectin and PAI-1 mRNA expression induced by TGF-beta1 were significantly inhibited by CTGF antisense oligodeoxynucleotide (ODN) transfection. With prolonged incubation time, CTGF antisense ODN also inhibited intracellular alpha-SMA and PAI-1 protein synthesis, lowered the level of fibronectin and PAI-1 protein secreted into the media, as confirmed by indirect immuno-fluorescence, flow cytometry, enzyme-linked immunosorbent assay (ELISA) and Western blot methods respectively. These results suggested that CTGF may play a crucial role in the renal tubular epithelial-transdifferentiation and the following deposition/degradation process of ECM during tubulointerstitial fibrosis.

Authors+Show Affiliations

Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zhangchun1234@hotmail.comNo 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

15135656

Citation

Zhang, Chun, et al. "Role of Connective Tissue Growth Factor in Renal Tubular Epithelial-myofibroblast Transdifferentiation and Extracellular Matrix Accumulation in Vitro." Life Sciences, vol. 75, no. 3, 2004, pp. 367-79.
Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in vitro. Life Sci. 2004;75(3):367-79.
Zhang, C., Meng, X., Zhu, Z., Yang, X., & Deng, A. (2004). Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in vitro. Life Sciences, 75(3), 367-79.
Zhang C, et al. Role of Connective Tissue Growth Factor in Renal Tubular Epithelial-myofibroblast Transdifferentiation and Extracellular Matrix Accumulation in Vitro. Life Sci. 2004 Jun 4;75(3):367-79. PubMed PMID: 15135656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in vitro. AU - Zhang,Chun, AU - Meng,Xianfang, AU - Zhu,Zhonghua, AU - Yang,Xiao, AU - Deng,Anguo, PY - 2004/01/06/received PY - 2004/02/26/accepted PY - 2004/5/12/pubmed PY - 2004/6/21/medline PY - 2004/5/12/entrez SP - 367 EP - 79 JF - Life sciences JO - Life Sci VL - 75 IS - 3 N2 - Connective tissue growth factor (CTGF) has been reported to play an important role in mediating the profibrotic effects of transforming growth factor-beta (TGF-beta) in the pathogenesis of renal fibrosis. To further elucidate the role of CTGF in renal tubular transdifferentiation and extracellular matrix (ECM) metabolism, we examined the time-course of CTGF, alpha-smooth muscle actin (alpha-SMA), fibronectin and plasminogen activator inhibitor-1(PAI-1) gene expression upon the stimulation of TGF-beta1 (5 microg/L) in cultured human proximal tubular epithelial cell line (HKC), and further investigated the effects of endogenous CTGF blockade. On reverse transcriptional-polymerase chain reaction (RT-PCR) analysis, TGF-beta1 upregulated CTGF gene expression, preceding that of alpha-SMA, fibronectin and PAI-1. The alpha-SMA, fibronectin and PAI-1 mRNA expression induced by TGF-beta1 were significantly inhibited by CTGF antisense oligodeoxynucleotide (ODN) transfection. With prolonged incubation time, CTGF antisense ODN also inhibited intracellular alpha-SMA and PAI-1 protein synthesis, lowered the level of fibronectin and PAI-1 protein secreted into the media, as confirmed by indirect immuno-fluorescence, flow cytometry, enzyme-linked immunosorbent assay (ELISA) and Western blot methods respectively. These results suggested that CTGF may play a crucial role in the renal tubular epithelial-transdifferentiation and the following deposition/degradation process of ECM during tubulointerstitial fibrosis. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/15135656/Role_of_connective_tissue_growth_factor_in_renal_tubular_epithelial_myofibroblast_transdifferentiation_and_extracellular_matrix_accumulation_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024320504002486 DB - PRIME DP - Unbound Medicine ER -