Inhibition of LINC00707/miR-223-3p/FKBP5 axis has a protective effect on diabetic kidney disease.

Abstract

Objective: Research indicates that LINC00707 is abnormally expressed in patients suffering from diabetic kidney disease (DKD). Nevertheless, the precise role of LINC00707 in the context of DKD remains enigmatic and warrants further investigation.

Methods: Initially, RT-qPCR was employed to assess the expression levels of LINC00707 in patients with DKD. Subsequently, we cultured glomerular podocytes under high-glucose conditions. The effects of LINC00707 on cell proliferation, apoptosis, podocyte functionality (Podocin, Nephrin, and CD2AP), oxidative stress (MDA and SOD), and inflammatory responses (IL-1β, IL-6, and TNF-α) were evaluated using CCK-8, flow cytometry, RT-qPCR, and ELISA assays. Finally, we co-regulated LINC00707 alongside its downstream targets to elucidate the molecular mechanisms by which LINC00707 influences podocyte injury.

Results: LINC00707 is abnormally upregulated in DKD patients. Furthermore, a notable inverse correlation has been observed between LINC00707 levels and renal function in these patients. Upon downregulating LINC00707, we observed an increase in cellular proliferative activity, alongside elevated levels of Podocin, Nephrin, and CD2AP. Concurrently, the reduction of LINC00707 was associated with decreased levels of MDA, as well as proinflammatory cytokines. Significantly, the inhibition of miR-223-3p was found to reverse these observed effects. Further investigation revealed that miR-223-3p directly targets FK506-binding protein 5 (FKBP5).

Conclusions: Inhibition of LINC00707 may reduce podocyte damage during hyperglycemia by targeting miR-223-3p/FKBP5.