Connective tissue growth factor stimulates renal cortical myofibroblast-like cell proliferation and matrix protein production.
Myofibroblasts primarily contribute to the pathogenesis of renal interstitial fibrosis by unregulated cell proliferation and synthesis of excessive amounts of extracellular matrix (ECM) proteins. We used cultured myofibroblast-like cells obtained by outgrowth from explants of rat kidney cortex to study the effects and relevant signaling pathway of connective tissue growth factor (CTGF) on cell proliferation and ECM production. Exogenous CTGF stimulated proliferation of myofibroblast-like cells in a dose- and time-dependent manner. CTGF also increased the secretion of fibronectin and collagen I protein in the supernatant medium. Nevertheless, CTGF did not affect matrix-degrading metalloproteinases-2 and -9 activities in supernatant medium measured by gelatin zymography. CTGF induced activation of extracellular signal-regulated protein kinase (ERK)1/2 mitogen-activated protein kinase pathway as early as 5 minutes. Inhibition of ERK1/2 activation with PD98059 completely blocked CTGF-induced cell proliferation as well as secretion of fibronectin and collagen I protein. The above results indicate that CTGF triggers cell proliferation and production of ECM proteins in cultured myofibroblast-like cells through the ERK1/2 mitogen-activated protein kinase pathway.
Gao
Xuxia
X
Division of Nephrology, First Hospital and Institute of Nephrology, Peking University, Beijing, China.
Li
Jingzi
J
Huang
Haichang
H
Li
Xiaomei
X
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004306:Dose-Response Relationship, Immunologic; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007668:Kidney / Q000166:cytology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats
D000911:Antibodies, Monoclonal; C526316:CCN2 protein, rat; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9