Glucan stimulates human dermal fibroblast collagen biosynthesis through a nuclear factor-1 dependent mechanism.

Glucan, an immunomodulator, has been reported to increase collagen deposition and tensile strength in experimental models of wound repair. Previous data suggest that glucan modulates wound healing via an indirect mechanism in which macrophages are stimulated to release growth factors and cytokines. However, recent data have shown the presence of glucan receptors on normal human dermal fibroblasts, suggesting that glucans may be able to directly stimulate fibroblast collagen biosynthesis. To test this hypothesis, we examined the effect of glucan on collagen biosynthesis in normal human dermal fibroblasts. We assessed nuclear factor-1 (NF-1) activation, procollagen mRNA expression, collagen biosynthesis, and whether there was a causal link between glucan treatment, NF-1 activation, and collagen expression. Glucan (1 microg/ml) increased NF-1 binding activity by 46% (8 hours), 64% (24 hours), 215% (36 hours), and 119% (48 hours) in cultured normal human dermal fibroblasts. Alpha 1(I) and alpha1 (III) procollagen mRNA were increased in glucan-treated normal human dermal fibroblasts when compared with the untreated fibroblasts. Collagen synthesis was increased at 24 hours and 48 hours following glucan treatment of normal human dermal fibroblasts. Down-regulation of NF-1 by pentifylline inhibited glucan-induced procollagen mRNA expression. These data indicate that glucan can directly stimulate human fibroblast collagen biosynthesis through an NF-1-dependent mechanism.