Hänsch G M, Wagner C, Bürger A, Dong W, Staehler G, Stoeck M
Institut für Immunologie, Universität Heidelberg, Germany.
J Cell Physiol. 1995 Jun;163(3):451-7. doi: 10.1002/jcp.1041630304.
The pathogenesis of glomerular scarring is multifactional; recent evidence suggests that transforming growth factor beta (TGF beta), a pleiotropic cicatricial mediator, may promote mesangial sclerosis by enhancing the production of extracellular matrix proteins. We studied the effect of TGF beta 1 and TFG beta 2 on collagen type IV and fibronectin (FN) synthesis in human glomerular mesangial cells in culture (GMC). Two hours after addition of TGF beta, an up to twofold increase in abundance of collagen type IV mRNA was found, which further increased up to fivefold within 24 h. Addition of cycloheximide did not inhibit the TGF beta effect, but caused by itself an up to twofold increase in the abundance of collagen type IV mRNA after 2 h. Together with collagen mRNA, the mRNA for FN and for platelet-derived growth factor (PDGF) was also enhanced. PDGF was found to enhance abundance of the collagen type IV and fibronectin mRNA in GMC. A neutralizing antibody to PDGF or a PDGF-antisense oligonucleotide partly inhibited the TGF beta-induced increase of collagen type IV mRNA, suggesting that TGF beta can affect the collagen type IV synthesis not only directly but also indirectly via the synthesis of PDGF.
肾小球瘢痕形成的发病机制是多因素的；最近的证据表明，转化生长因子β（TGFβ），一种多效性的瘢痕形成介质，可能通过增强细胞外基质蛋白的产生来促进系膜硬化。我们研究了TGFβ1和TGFβ2对培养的人肾小球系膜细胞（GMC）中IV型胶原和纤连蛋白（FN）合成的影响。加入TGFβ2小时后，发现IV型胶原mRNA丰度增加了两倍，在24小时内进一步增加至五倍。加入放线菌酮并不抑制TGFβ的作用，但自身在2小时后可使IV型胶原mRNA丰度增加两倍。与胶原mRNA一起，FN和血小板衍生生长因子（PDGF）的mRNA也增加。发现PDGF可增强GMC中IV型胶原和纤连蛋白mRNA的丰度。抗PDGF中和抗体或PDGF反义寡核苷酸部分抑制了TGFβ诱导的IV型胶原mRNA增加，提示TGFβ不仅可直接影响IV型胶原合成，还可通过PDGF合成间接影响。
