CTGF Contributes to the Development of Posterior Capsule Opacification: an in vitro and in vivo study

Int J Biol Sci. 2018 Mar 11;14(4):437-448. doi: 10.7150/ijbs.23946. eCollection 2018.

Abstract

Connective tissue growth factor (CTGF) is a crucial factor that plays a major role in the process of posterior capsule opacification (PCO). However, the effects of CTGF on the proliferation and migration of lens epithelial cells (LECs) and on the mechanism of the epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) in human lens epithelial cells (HLECs) as well as the effects of shRNA-mediated CTGF knockdown on the development of PCO in rats remain unclear. In the present study, we found that CTGF promoted EMT, proliferation, migration and the expression of p-ERK1/2 protein in HLECs but exerted little effect on the expression of p-p38 and p-JNK1/2 proteins. MEK inhibitor U0126 effectively restrained the CTGF-induced expression of α-smooth muscle actin (α-SMA), fibronectin (Fn) and type I collagen (COL-1) in HLECs. CTGF knockdown effectively postponed the onset of PCO in the rats and significantly reduced the expression of α-SMA in the capsule. In conclusion, CTGF contributed to the development of PCO presumably by promoting proliferation, migration of LECs, EMT specific protein expression and ECM synthesis in HLECs, which is dependent on ERK signalling. Furthermore, blocking CTGF effectively inhibited PCO in the rats and the EMT specific protein expression in the lens capsule.

Keywords: CTGF; ERK signalling; Epithelial Mesenchymal Transition; Extracellular Matrix; Posterior Capsule Opacification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Connective Tissue Growth Factor / physiology*
  • Epithelial Cells
  • Gene Knockdown Techniques
  • Humans
  • Lens, Crystalline / cytology
  • MAP Kinase Signaling System / genetics
  • Posterior Capsule of the Lens / pathology*
  • RNA Interference
  • Rats
  • Swine

Substances

  • Connective Tissue Growth Factor