Effects of Apelin on the fibrosis of retinal tissues and Müller cells in diabetes retinopathy through the JAK2/STAT3 signalling pathway

Abstract

Retinal fibrosis was a key characteristic of diabetes retinopathy (DR). Apelin was found to be a candidate for tissue fibrosis. Nevertheless, the role of Apelin in the Müller cells in DR remains unclear. This study identified the function and mechanism of Apelin in Müller cells and the fibrosis of retinal tissue. Western blot was carried out to detect the Apelin, GFAP, Collagen I, α-SMA, JAK2 and STAT3 protein levels. Masson staining was performed to display the histopathological changes in retinal tissue of diabetic mellitus (DM) rats. The immunofluorescence staining was conducted to evaluate the Apelin levels in the retinal tissue. The levels of GFAP, Collagen I and α-SMA in the retinal tissue of DM rats was visualised by the immunohistochemistry staining. The results showed that Apelin, GFAP, Collagen I andα-SMA expression was prominently elevated in the retinal tissue of DM rats and high glucose (HG)-exposed Müller cells. The results of Masson staining showed that the epiretinal fibrotic membrane was observed in DM rats. Apelin knockdown declined the GFAP, Collagen I andα-SMA levels. Besides, the protein levels of p-JAK2 and p-STAT3 were elevated in the HG-treated Müller cells, while Apelin knockdown declined them. FLLL32 treatment neutralised the role of Apelin. In conclusion, Apelin facilitated the fibrogenic activity of Müller cells through activating the JAK2/STAT3 signalling pathway, and thus inducing the retinal fibrosis in DR.

Keywords:

• Apelin
• Müller cells
• fibrosis
• diabetes retinopathy
• JAK2/STAT3

Acknowledgments

Not applicable.

Authors’ contributions

All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. Y L drafted the work and revised it critically for important intellectual content; Q H and B W were responsible for the acquisition, analysis, or interpretation of data for the work

Availability of data and materials

All data included in this study are available upon request by contact with the corresponding author.

Disclosure statement

All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare.

Ethics approval and consent to participate

The animal experimental protocol was approved by the Medical Ethics Committee of Eye Institute and Affiliated Xiamen Eye Centre of Xiamen University.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (grant No.81900881) from the National Natural Science Foundation Committee; Natural Science Foundation of Youth Innovation Program of Fujian Province (grant No.2020D028); Xiamen Science and Technology Planning Project (grant No.3502Z20184023); Natural Science Foundation Program of Fujian Province (grant No.2023j011584).