# LAMC1 aggravates diabetic retinopathy through PI3K/AKT signaling-regulated epithelial-mesenchymal transition in retinal pigment epithelial cells

## TL;DR

LAMC1 worsens diabetic retinopathy by triggering cell changes through the PI3K/AKT signaling pathway in retinal cells.

## Contribution

This study identifies LAMC1 as a novel driver of diabetic retinopathy via PI3K/AKT-regulated EMT in RPE cells.

## Key findings

- LAMC1 is significantly upregulated in high glucose-treated RPE cells and diabetic mouse retinas.
- LAMC1 promotes EMT and cell migration via PI3K/AKT activation in RPE cells.
- LAMC1 knockdown reduces retinal damage in diabetic mice.

## Abstract

Diabetic retinopathy (DR), a leading cause of adult blindness, with LAMC1-mediated epithelial-mesenchymal transition (EMT) playing a key role. By analyzing DR-related microarray datasets (GSE60436/GSE102485) from GEO, we identified 685 differentially expressed genes (570 downregulated, 115 upregulated). Functional and WGCNA analyses linked these to PI3K/Akt signaling, revealing 11 diagnostic hub genes, including LAMC1. Western blot analysis confirmed that LAMC1 significantly upregulated in high glucose (HG)-treated ARPE-19 cells and diabetic mouse retinas. In vitro and in vivo experiments confirmed that LAMC1 promotes EMT in retinal pigment epithelial (RPE) cells via PI3K/Akt activation, enhancing migration and invasion. Conversely, LAMC1 knockdown alleviated retinal damage in diabetic mice. Our studies uncovered that LAMC1’s role in DR progression through PI3K/Akt-driven EMT, suggesting its potential as a therapeutic target.

•LAMC1 promotes diabetic retinopathy through epithelial-mesenchymal transition regulated by PI3K/AKT signaling axis.

LAMC1 promotes diabetic retinopathy through epithelial-mesenchymal transition regulated by PI3K/AKT signaling axis.