Transforming growth factor‐β isoforms differently stimulate proα2 (I) collagen gene expression during wound healing process in transgenic mice

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Abstract
The role of many growth factors and cytokines in the process of wound healing has been intensively investigated in recent two decades. Among them, transforming growth factor‐βs (TGF‐βs) are well known to have a potent stimulatory effect on collagen synthesis as shown in various in vivo experimental systems. In the present study, we examined the effects of various growth factors on the promoter activity of the proα2 (I) collagen gene (COL1A2) during the wound healing process. For this purpose, we utilized transgenic mice harboring the −17 kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase or a bacterial β‐galactosidase gene. These mice exhibited normal phenotypic expression and the wound healing process was not impaired. Full thickness wounds were made by punch biopsy. We examined the effects of TGF‐β1, ‐β2, ‐β3, basic fibroblast growth factor, platelet‐derived growth factor, and connective tissue growth factor by applying them locally to the open wound every 2 days. Among the growth factors examined, all of the three isoforms of TGF‐β exhibited a more potent stimulatory effect on COL1A2 promoter activity than did other factors. In addition, while TGF‐β1 and ‐β2 significantly increased the number of fibroblasts which were positive for X‐Gal staining, TGF‐β3 treatment did not change the number of β‐galactosidase expressing cells. Accumulation of collagen fibers was observed to the same extent in the mice treated with TGF‐β1 and those with TGF‐β3. These findings suggest that TGF‐β1 and ‐β3 have similar but not identical regulatory mechanisms of COL1A2 expression, and that their pathophysiological roles in wound healing might be different from each other. J. Cell. Physiol. 190: 375–381, 2002.