N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress

Abstract

Müller cells (MCs) represent the major glial cells that are responsible for maintaining retinal homeostasis. In diabetic retinopathy, Müller cell activation occurs in the initial stages, playing a role in many pathological processes, such as neovascularization, neuronal dysfunction, and inflammatory retinal environment. As the most common RNA modification in eukaryotes, N⁶-methyladenosine (m⁶A) exerts dynamic and reversible control over cellular functions in the context of high glucose (HG) stress. Here, we performed combined m⁶A and RNA sequencing to elucidate the landscape of m⁶A modification in MCs under HG environmental stimuli. The potential functions of aberrant m⁶A peaks and differentially expressed genes were analyzed using bioinformatics analysis. Our findings indicate that m⁶A modification may regulate the expression of heat shock proteins (HSPs) 70 isoforms HSPA1A and HSPA1B, which are stress-inducible chaperones critical for cell survival under adverse conditions, including hyperglycemia. Modulating m⁶A modification may regulate critical gene expression and cellular functions of MCs under HG stress.