TRANSFORMING GROWTH FACTOR-BETA REVERSES THE GLUCOCORTICOID-INDUCED WOUND-HEALING DEFICIT IN RATS - POSSIBLE REGULATION IN MACROPHAGES BY PLATELET-DERIVED GROWTH-FACTOR
TRANSFORMING GROWTH FACTOR-BETA REVERSES THE GLUCOCORTICOID-INDUCED WOUND-HEALING DEFICIT IN RATS - POSSIBLE REGULATION IN MACROPHAGES BY PLATELET-DERIVED GROWTH-FACTOR
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DOI：
10.1073/pnas.86.7.2229
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发表时间：
1989-04-01
影响因子：
11.1
通讯作者：
DEUEL, TF
中科院分区：
文献类型：
--
作者：
PIERCE, GF;MUSTOE, TA;DEUEL, TF
转化生长因子。β。(转化生长因子--β。)而血小板衍生生长因子(PDGF)是一种有效的有丝分裂多肽，可以提高实验动物的伤口愈合率；相比之下，糖皮质激素则抑制伤口修复。转化生长因子-β的潜能。在皮肤创伤强度下降50%的甲基强的松龙治疗的大鼠身上，测试了PDGF逆转这种愈合抑制的作用。单次应用转化生长因子-β。(每个伤口10-40 pmol，0.25-1微克)在受伤时局部应用，以浓度依赖和高度重复性的方式完全逆转这一缺陷。用糖皮质激素治疗的动物创面的特点是几乎完全没有中性粒细胞和巨噬细胞，以及成纤维细胞的延迟流入和密度降低；然而，用转化生长因子-β治疗的这种创面。显示创面成纤维细胞和细胞内I型前胶原显著增加，PDGF不能逆转糖皮质激素处理的大鼠伤口断裂强度的下降；PDGF处理的创面有更多的成纤维细胞，但这些成纤维细胞缺乏在转化生长因子-β处理的创面中发现的I型前胶原的增强表达。正常组织修复所需的伤口巨噬细胞在接受糖皮质激素治疗的动物的PDGF和转化生长因子-β治疗的创面中仍然缺失。这一结果表明，巨噬细胞可能在PDGF处理的创面成纤维细胞中作为诱导前胶原合成的中介细胞，并且转化生长因子-β。可能通过其直接刺激成纤维细胞合成I型前胶原的能力绕过巨噬细胞。虽然PDGF不刺激前胶原的合成，但在啮齿动物巨噬细胞系中，PDGF诱导了非常显著的、随时间变化的转化生长因子-β的表达增强。
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 .mu.g) applied locally at the time of wounding fully reversed this deficit in a concentration-dependent and highly reproducible manner. Wounds in gluocorticoid-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.