Pterygium is a common ocular disease with high recurrence rate, characterized by hyperplasia of subconjunctival fibrovascular tissue. Autophagy, the important process to maintain cellular homeostasis, participates the pathogenic fibrosis of different organs. However, the exact role of autophagy in pterygium pathogenesis remains unknown. Here we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues. The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts (ConFB) treated with TGF-β1, evidenced by increased fibrotic level and strong proliferative and invasive capability. The autophagic activity was suppressed during TGF-β1 or ultraviolet-induced fibrosis of ConFB. Activating autophagy dramatically retarded the fibrotic progress of ConFB, while blocking autophagy exacerbated this process. Furthermore, SQSTM1, the main cargo receptor of selective autophagy, was found to significantly promote the fibrosis of ConFB through activating PKCι-NF-κB signaling pathway. Knockdown of SQSTM1, PKCι, or p65 in ConFB delayed the TGF-β1-induced fibrosis. Over-expression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on the TGF-β1-induced fibrosis. Collectively, our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating SQSTM1-PKCι-NF-κB signaling cascades. This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.
Keyphrases
- signaling pathway
- cell death
- pi k akt
- endothelial cells
- epithelial mesenchymal transition
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- high glucose
- transforming growth factor
- diabetic rats
- induced pluripotent stem cells
- gene expression
- risk assessment
- pluripotent stem cells
- drug induced
- poor prognosis
- inflammatory response
- idiopathic pulmonary fibrosis
- electronic health record
- machine learning
- immune response
- lps induced
- density functional theory
- extracellular matrix
- newly diagnosed