Insulin-like Growth Factor Binding Protein 7 Inhibits HaCaT Cell Growth By Modulating TGF-β1 Signaling

Background Insulin-like growth factor-binding protein 7 (IGFBP7) has been found to be one of several keratinocyte (KC)-specific genes. A global gene expression study revealed that IGFBP7 is downregulated in the psoriatic epidermis. In the previous study, effects of IGFBP7 downregulation on transforming growth factorβ(TGF-β) were detected, however, the exact mechanism still remained unclear.Objective To systematically assess the role of IGFBP7 in the regulation of psoriasis, and the molecular mechanism responsible for the divergent effects involved in TGF-βpathway, the correlation of IGFBP7 with transforming growth factorβ1 (TGF-β1) and p38 mitogen activated protein kinase(p38 MAPK) activity was examined.Methods HaCaT cell is a spontaneously immortalized human keratinocyte line. We used IGFBP7-specific small interfering RNA (siRNA) or recombinant IGFBP7 (rIGFBP7) in HaCaT cells to model IGFBP7 downregulation or upregulation in vitro. Immunocytochemistry was used to examine IGFBP7 and TGF-β1 expression. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and annexin V/PI assay were investigated. Western blotting was also used to examine p38-MAPK activity.Results Downregulation of IGFBP7 was found to markedly enhance HaCaT proliferation, which was associated with a significant decrease in HaCaT apoptosis. Furthermore, recombinant IGFBP7 could reverse the effects. The upregulation of TGF-β1 and the phosphorylation of MAPK were investigated in IGFBP7-depleted cells. And the contrary results were found in IGFBP7-overexpressed cells.Conclusions Our data explore that IGFBP7 maybe influence TGF-(31 regulation through MAPK pathway in HaCaT cells, which provide a clue for the treatment of hyperproliferative dermatoses.