TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells.
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.
Gore-Hyer
Elizabeth
E
Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston 29425, USA.
Shegogue
Daniel
D
Markiewicz
Malgorzata
M
Lo
Shianlen
S
Hazen-Martin
Debra
D
Greene
Eddie L
EL
Grotendorst
Gary
G
Trojanowska
Maria
M
D000256:Adenoviridae / Q000235:genetics; D019138:Antibodies, Blocking / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D005822:Genetic Vectors; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D019138:Antibodies, Blocking; C526317:CCN2 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D011392:Proline; D008156:Luciferases