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Am J Physiol Renal Physiol 283: F707-F716, 2002. First published May 14, 2002; doi:10.1152/ajprenal.00007.2002
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Vol. 283, Issue 4, F707-F716, October 2002

TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells

Elizabeth Gore-Hyer1, Daniel Shegogue1, Malgorzata Markiewicz1, Shianlen Lo1, Debra Hazen-Martin2, Eddie L. Greene3, Gary Grotendorst4, and Maria Trojanowska1

Divisions of 1 Rheumatology and Immunology and 3 Nephrology, 2 Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425; and 4 Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33136

Transforming growth factor-beta (TGF-beta ) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-beta and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-beta and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, alpha 2(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-beta and CTGF in HMCs. However, only TGF-beta stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-beta and CTGF, although TGF-beta was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.

mesangial cells; tubule epithelial cells; collagen; tenascin; epithelial-mesenchymal transdifferentiation; connective tissue growth factor; transforming growth factor-beta


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