Pierce G F, Mustoe T A, Lingelbach J, Masakowski V R, Gramates P, Deuel T F
Department of Pathology, Jewish Hospital, Washington University Medical Center, Saint Louis, MO 63110.
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2229-33. doi: 10.1073/pnas.86.7.2229.
Transforming growth factor beta (TGF-beta) and the platelet-derived growth factor (PDGF) are potent mitogenic polypeptides which enhance rates of wound healing in experimental animals; in contrast, glucocorticoids inhibit wound repair. The potential of TGF-beta and PDGF to reverse this inhibition in healing was tested in methylprednisolone-treated rats with deficits in skin wound strength of 50%. Single applications of TGF-beta (10-40 pmol per wound, 0.25-1 micrograms) applied locally at the time of wounding fully reversed this deficit in a concentration-dependent and highly reproducible manner. Wounds in glucocorticoid-treated animals were characterized by a near total absence of neutrophils and macrophages and by a delayed influx and reduced density of fibroblasts; however, such wounds treated with TGF-beta showed significant increases in wound fibroblasts and in intracellular procollagen type I. PDGF did not reverse the deficit in wound breaking strength in glucocorticoid-treated rats; there were more fibroblasts in the PDGF-treated wounds, but these fibroblasts lacked the enhanced expression of procollagen type I found in TGF-beta-treated wounds. The wound macrophages, required for normal tissue repair, remained absent from both PDGF- and TGF-beta-treated wounds in glucocorticoid-treated animals. This result suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of procollagen type I in fibroblasts. Whereas PDGF does not stimulate procollagen synthesis, in a rodent macrophage cell line, PDGF induced a highly significant, time-dependent enhancement of expression of TGF-beta.
转化生长因子β（TGF-β）和血小板衍生生长因子（PDGF）是强效的有丝分裂原性多肽，可提高实验动物的伤口愈合速度；相比之下，糖皮质激素会抑制伤口修复。在甲基强的松龙治疗的大鼠中，测试了TGF-β和PDGF逆转这种愈合抑制作用的潜力，这些大鼠的皮肤伤口强度有50%的缺陷。在伤口形成时局部单次应用TGF-β（每个伤口10 - 40皮摩尔，0.25 - 1微克）以浓度依赖性和高度可重复的方式完全逆转了这种缺陷。糖皮质激素治疗动物的伤口特征是几乎完全没有中性粒细胞和巨噬细胞，成纤维细胞的流入延迟且密度降低；然而，用TGF-β处理的此类伤口显示伤口成纤维细胞和细胞内I型前胶原显著增加。PDGF并没有逆转糖皮质激素治疗大鼠伤口抗张强度的缺陷；PDGF处理的伤口中有更多的成纤维细胞，但这些成纤维细胞缺乏在TGF-β处理的伤口中发现的I型前胶原表达增强。糖皮质激素治疗动物的PDGF和TGF-β处理的伤口中都没有正常组织修复所需的伤口巨噬细胞。这一结果表明，巨噬细胞可能通常在PDGF处理伤口的成纤维细胞中I型前胶原合成的诱导过程中起中间作用，并且TGF-β可能通过其直接刺激成纤维细胞中新的I型前胶原合成的能力绕过巨噬细胞。虽然PDGF不刺激前胶原合成，但在啮齿动物巨噬细胞系中，PDGF诱导TGF-β表达高度显著的、时间依赖性增强。
