Open AccessFollistatin-like protein 1 functions as a potential target of gene therapy in proliferative diabetic retinopathy
Author(s) -
Rui Niu,
Zetong Nie,
Lin Liu,
Yu-Wen E. Chang,
Jian-Qun Shen,
Qiong Chen,
Lijie Dong,
BinJie Hu
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202678
Subject(s) - ctgf , follistatin , vascular endothelial growth factor , extracellular matrix , diabetic retinopathy , growth factor , gene silencing , fibrosis , downregulation and upregulation , cancer research , vascular endothelial growth factor a , medicine , bioinformatics , gene , biology , endocrinology , receptor , microbiology and biotechnology , diabetes mellitus , vegf receptors , genetics
The degree of retinal fibrosis increased in proliferative diabetic retinopathy (PDR) patients after administration of anti-Vascular endothelial growth factor (VEGF) injections. Previous studies showed that the balance between connective tissue growth factor (CTGF) and VEGF plays an important role. Therefore, in a high-glucose state, an anti-VEGF and CTGFshRNA dual-target model was used to simulate clinical dual-target treatment in PDR patients, and RNA sequencing (RNA-Seq) technology was used for whole transcriptome sequencing. A hypoxia model was constructed to verify the sequencing results at the cellular level, and the vitreous humor and proliferative membranes were collected from patients for verification. All sequencing results included Follistatin-like protein 1 ( FSTL1 ) and extracellular matrix (ECM) receptor pathway, indicated that anti-VEGF therapy may upregulate FSTL1 expression, while dual-target treatment downregulated FSTL1. Thus, we further studied the function of FSTL1 on the expression of VEGF and ECM factors by both overexpressing and silencing FSTL1 . In conclusion, our results suggested that FSTL1 may be involved in the pathogenesis of PDR and is related to fibrosis caused by the anti-VEGF treatment, thus providing a potential target for gene therapy in PDR.