Enhancement of the granulation tissue formation in hairless mice by a potent vitamin D receptor agonist--KH 1060.
KH 1060 is a 20-epi analogue of 1,25-dihydroxyvitamin D3 and a potent agonist of the vitamin D receptor. Our recent finding that it stimulates glycosaminoglycan synthesis and transforming growth factor-beta 1 (TGF-beta 1) expression in normal skin provided a rationale for investigating its influence on the process of wound healing. Normal and betamethasone-impaired granulation tissue formation was studied in a polytetrafluoroethylene dead space model in hairless mice. The application of KH 1060 increased the indexes of fibroplasia and cellularity ([3H]thymidine incorporation and DNA concentration) of the betamethasone-impaired granulation tissue. Collagen production and deposition, measured as hydroxyproline synthesis and concentration in the granulation tissue, were also increased. The effect of KH 1060 on normal connective tissue repair was less pronounced; DNA and hydroxyproline concentrations in granulation tissue were unchanged. KH 1060 strongly stimulated the expression of TGF-beta 1 in betamethasone-impaired granulation tissue. Thus, it effectively reversed the deleterious effect of betamethasone on granulation tissue. The hyperproliferative response to this vitamin D analogue might be related to the direct stimulation of the vitamin D receptors in the granulation tissue, while the increased collagen synthesis and deposition was probably caused indirectly, via stimulation of TGF-beta 1.
Gniadecki
R
R
Department of Dermatological Research, Leo Pharmaceutical Products, Ballerup, Denmark.
Serup
J
J
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006097:Granulation Tissue / Q000166:cytology*; D051379:Mice; D008812:Mice, Hairless; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects*
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D016212:Transforming Growth Factor beta; C074279:KH 1060; D001623:Betamethasone; D002117:Calcitriol