Tacrolimus fails to regulate collagen expression in dermal fibroblasts.

Abstract Background The purpose of this study was to investigate the effects of tacrolimus on human fibroblasts derived from unwounded skin, hypertrophic scars (HTS), and keloids. We hypothesized that tacrolimus, a potent anti-inflammatory and immunosuppressant drug known to attenuate solid organ transplant fibrosis, would block collagen expression in human dermal fibroblasts. Methods We performed genomewide microarray analysis on human dermal fibroblasts treated with tacrolimus in vitro . We used principal component analysis and hierarchical clustering to identify targets regulated by tacrolimus. We performed quantitative polymerase chain reaction to validate the effect of tacrolimus on collagen 1 and 3 expression. Results We identified 62, 136, and 185 gene probes on microarray analysis that were significantly regulated ( P P Conclusions Tacrolimus does not modulate the expression of collagen 1 or 3 in human dermal fibroblasts in vitro . Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 are blocked by tacrolimus in pathologic fibroblasts but not normal fibroblasts, and may represent novel genes underlying HTS and keloid pathogenesis. Tacrolimus-based anti-fibrotics might prove more effective if non-fibroblast populations such as inflammatory cells and keratinocytes are targeted.