Platelet-derived growth factor-BB induces renal tubulointerstitial myofibroblast formation and tubulointerstitial fibrosis.

作者：Winson W. Tang, TR Ulich, Dave Lacey, Dave Hill, Qi Mei, Stephen A. Kaufman, Gwyneth Y. Van, John E. Tarpley, Jerry Yee · 发表于：PubMed · 年份：1996 · 被引用次数：227 · 研究领域：Kidney Stones and Urolithiasis Treatments、Chronic Kidney Disease and Diabetes、Abdominal Trauma and Injuries

Tubulointerstitial fibrosis correlates closely with renal function, although the mechanism regulating tubulointerstitial fibrogenesis remains poorly understood. Since platelet-derived growth factor (PDGF) is a growth factor for fibroblasts, we examined the effect of daily (for 7 days) PDGF-AA or PDGF-BB administration on renal tubulointerstitial architecture in rats. PDGF-AA administration at a dose of 5 mg/kg did not affect the renal tubulointerstitium. By comparison, PDGF-BB induced dose-dependent renal tubulointerstitial cell proliferation and fibrosis. At 5 mg/kg, PDGF-BB increased BrdU labeling in tubulointerstitial fibroblasts at 24 hours (19-fold), which peaked at 72 hours (23-fold) with bromodeoxyuridine uptake returning to control values by 7 days. Tubulointerstitial proliferation was associated with the differentiation of these cells into myofibroblasts as evidenced by alpha-smooth muscle actin expression beginning on day 3. The expression of alpha-smooth muscle actin peaked on day 5 and had markedly declined by day 21. In addition, apoptotic cells were identified within the tubulointerstitium on day 3 and progressively increased through day 7, suggesting that the disappearance of myofibroblasts may have occurred through apoptosis. These changes were accompanied by increased expression of alpha 1 (III) collagen mRNA and interstitial accumulation of type III collagen within the renal cortex. By morphometric analysis, an approximately twofold increase in collagen III ...