Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is an important microvascular complication of diabetes, and one of the leading causes of end-stage kidney disease. However, the mechanism of the DN pathogenic process remains unclear. Recently, long non-coding (lnc)RNA dysregulation has been regarded to cause the occurrence and development of various human diseases, although the functions of lncRNAs in human DN are poorly understood. The authors' previous study using microarray analysis identified hundreds of dysregulated lncRNAs in DN, although the functions of these lncRNAs were not demonstrated. Out of those dysregulated lncRNAs, Gm5524 was significantly upregulated in response to DN, while Gm15645 was significantly downregulated in response to DN. In the present study, this result was further validated by reverse transcription-quantitative polymerase chain reaction assays, and downregulating or overexpressing Gm5524 and Gm15645 in mouse podocytes. Notably, knockdown of Gm5524 and overexpression of Gm15645 induced mouse podocyte apoptosis and decreased cell autophagy in high-glucose culture conditions. In conclusion, the results of the present study revealed the roles of lncRNAs Gm5524 and Gm15645 in high-glucose induced podocyte apoptosis and autophagy during DN, which may further the understanding of the involvement of lncRNAs in DN, and provide a potential novel therapeutic target for this disease.

<p>Curcumin Inhibited Podocyte Cell Apoptosis and Accelerated Cell Autophagy in Diabetic Nephropathy via Regulating Beclin1/UVRAG/Bcl2</p>

“…Apoptosis was a process whereby cells died in a controlled manner, which was involved in the development of DN. 39,40 Podocyte apoptosis is an important pathogenic alteration that leads to podocyte loss in DN. Previous studies have shown that the interaction between apoptosis and DN included complex pathways and molecular and confirmed the important role of apoptosis pathways in DN.…”

SGLT2 Inhibitor Empagliflozin and DPP4 Inhibitor Linagliptin Reactivate Glomerular Autophagy in db/db Mice, a Model of Type 2 Diabetes

“…The mechanisms of autophagy suppression in diabetic kidneys remain a matter of debate. Hyperglycemia was considered an autophagy suppressor in the studies with cultured podocytes [24,35], glomerular endothelial cells [36] and mesangial cells [37]. Kidney macroautophagy is regulated by mammalian target of rapamycin (mTOR) [8,38,39], AMP-activated protein kinase (AMPK) [8], SIRT1 [8], Wnt/β-catenin [40], and TGF-β [41] signaling pathways.…”

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

“…In terms of renal autophagy and apoptosis, lncRNA GM5524 expression was increased in DN mice and regulated these processes, upon stimulation with high glucose (Feng et al, 2018). GM5524 inhibits anti-apoptotic BCL2 expression and activates the LC3/ATG signaling pathway to promote autophagy (Feng et al, 2018).…”

“…In terms of renal autophagy and apoptosis, lncRNA GM5524 expression was increased in DN mice and regulated these processes, upon stimulation with high glucose (Feng et al, 2018). GM5524 inhibits anti-apoptotic BCL2 expression and activates the LC3/ATG signaling pathway to promote autophagy (Feng et al, 2018). LncRNA GAS5 is also a proapoptotic lncRNA, in which GAS5 promoted the human renal tubular epithelial cells apoptosis under high glucose environment (Lv et al, 2019) In contrast to that, lncRNA GM15645 expression was low in DN mice and podocyte cells upon stimulation of high glucose, and this lncRNA acts opposite to lncRNA GM5524 in the regulation of podocyte cells apoptosis and autophagy (Feng et al, 2018).…”