IL-22/IL-22RA1 promotes human Tenon's capsule fibroblasts proliferation and regulates fibrosis through STAT3 signaling pathway

Abstract

The study is aimed to investigate that the IL-22/IL-22RA1 signaling pathway regulates scar formation. A total of 31 glaucoma patients who had been previously treated with trabeculectomy surgery and the intraocular pressure was uncontrollable because of scarring and 19 strabismus patients as control patient group. ELISA showed that the IL-22 content of serum from glaucoma patients was 29.80{+/-}5.1 ng/l which is higher than that 5.21{+/-}0.9 ng/l from healthy group significantly. Serum from patients was used to incubate human Tenons capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and western blot result showed that IL-22 mediates the biological function of HTFs cells via binding IL-22RA1 directly. When transfection of siR-IL-22RA1 or IL-22RA1 gene, the HTFs cells shown significantly anti-fibrosis or pro-fibrosis separately. By using STAT3 inhibitor BAY in IL-22RA1 overexpression group, IL-22-induced proliferation were reduced in HTFS cells. IL-22 promoted fibroblasts cell proliferation and -SMA via IL-22/IL-22RA1/STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis. This results also show the novel factor in process of postoperative scarring. Summary StatementThe present study suggested that IL-22 expression in glaucoma patient after surgery. IL-22/IL-22RA1 signaling pathway promoted fibroblasts cell proliferation and -SMA by activating the STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis.