Systemic sclerosis (SSc) is a
connective tissue disease of unknown etiology. A hallmark of SSc is
fibrosis of the skin and internal organs. We recently demonstrated increased expression of
IGFBP-3 and
IGFBP-5 in primary cultures of fibroblasts from the skin of patients with SSc. In vitro,
IGFBP-3 and
IGFBP-5 induced a fibrotic phenotype and
IGFBP-5 triggered dermal
fibrosis in mice. To assess the ability of IGFBPs to trigger
fibrosis, we used an ex vivo human skin organ culture model. Our findings demonstrate that
IGFBP-3 and
IGFBP-5, but not
IGFBP-4, increase dermal and
collagen bundle thickness in human skin explants, resulting in substantial dermal
fibrosis and thickening. These fibrotic effects were sustained for at least two weeks. Our findings demonstrate that human skin ex vivo is an appropriate model to assess the effects of
fibrosis-inducing factors such as IGFBPs, and for evaluating the efficacy of inhibitors/
therapies to halt the progression of
fibrosis and potentially reverse it.