ENHANCEMENT OF THE GRANULATION-TISSUE FORMATION IN HAIRLESS MICE BY APOTENT VITAMIN-D RECEPTOR AGONIST - KH-1060

KH 1060 is a 20-epi analogue of 1,25-dihydroxyvitamin D-3 and a potent agonist of the vitamin D receptor. Our recent finding that it stimula tes glycosaminoglycan synthesis and transforming growth factor-beta 1 (TGF-beta 1) expression in normal skin provided a rationale for invest igating its influence on the process of wound healing. Normal and beta methasone-impaired granulation tissue formation was studied in a polyt etrafluoroethylene dead space model in hairless mice. The application of KH 1060 increased the indexes of fibroplasia and cellularity ([H-3] thymidine incorporation and DNA concentration) of the betamethasone-im paired granulation tissue. Collagen production and deposition, measure d as hydroxyproline synthesis and concentration in the granulation tis sue, were also increased. The effect of KH 1060 on normal connective t issue repair was less pronounced; DNA and hydroxyproline concentration s in granulation tissue were unchanged. KH 1060 strongly stimulated th e expression of TGF-beta 1 in betamethasone-impaired granulation tissu e. Thus, it effectively reversed the deleterious effect of betamethaso ne on granulation tissue. The hyperproliferative response to this vita min D analogue might be related to the direct stimulation of the vitam in D receptors in the granulation tissue, while the increased collagen synthesis and deposition was probably caused indirectly, via stimulat ion of TGF-beta 1.