Role of the long noncoding RNA H19 in TGF-β1-induced Tenon's capsule fibroblast proliferation and extracellular matrix deposition

Abstract

Glaucoma filtration surgery (GFS) is a classic surgical method used to treat glaucoma, the second leading cause of blindness. Scar formation caused by excessive Tenon's capsule fibroblast activation leads to surgical failure. However, the mechanism underlying this activation is largely unknown. In this study, we first isolated primary human Tenon's capsule fibroblasts (HTFs) and found that TGF-β promoted the viability, proliferation and extracellular matrix (ECM) deposition of HTFs. Then, we showed that TGF-β promoted the expression of H19 in HTFs and that suppression of H19 inhibited the effect of TGF-β on HTFs. Furthermore, we revealed that H19 exerted its effects by interacting with miR-200a in TGF-β-treated HTFs. Additionally, we showed that β-catenin was a target of miR-200a in TGF-β-treated HTFs. We also demonstrated that H19 acted by modulating the H19/miR-200a/β-catenin regulatory axis in TGF-β-treated HTFs. Ultimately, we found that the components of the H19/miR-200a/β-catenin regulatory axis were aberrantly expressed in a rat model of GFS. Our results show that H19 indeed acts by modulating β-catenin expression via miR-200a in TGF-β-treated HTFs, thus providing a novel rationale for the development of H19-based strategies to attenuate scar formation after GFS.