Abstract

Purpose Secreted protein acidic and rich in cysteine (SPARC), a matricellular glycoprotein , has been found to regulate processes involved in fibrotic diseases. The aim of this study was to investigate the anti-fibrotic effects of SPARC in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. Methods The expression of SPARC in HPFs was knocked down by RNA interference-based approach. Subsequently, we examined the expression of profibrotic markers induced by transforming growth factor-β1 (TGF-β1), including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin (FN). The changes in signaling pathways and matrix metalloproteinases (MMPs) were also detected by western blotting . The cellular migration ability, proliferation ability, apoptosis, and contractile phenotype were detected using the wound healing assay , Cell Counting Kit-8 assay, flow cytometry, and collagen gel contraction assay, respectively. The interaction between SPARC and TGF-β RII was detected by Co-IP Results Silencing of SPARC inhibited the basal and TGF-β1-induced expression of COL1, α-SMA, and FN in HPFs, and suppressed the expression of p-Smad2, p-Smad3, Smad4 and MMP2 , MMP9 . The downregulation of SPARC also attenuated the cell migration and contractile phenotype of HPFs. SPARC could bind to TGF-βRII under TGF-β1 treatment. However, knockdown of SPARC did not affect the proliferation and apoptosis of HPFs. Conclusion SPARC knockdown attenuated the fibrotic effect induced by TGF-β1 at least in part by inactivating the Smad2/3 pathways in HPFs. Therefore, SPARC may be a promising therapeutic target for the treatment of pterygium.