Circular RNA HIPK3 exacerbates diabetic nephropathy and promotes proliferation by sponging miR-185

Area of Science:

• Molecular Biology
• Renal Physiology
• RNA Biology

Background:

• Diabetic nephropathy (DN) is a serious complication of diabetes, characterized by kidney damage.
• Circular RNAs (circRNAs) are increasingly recognized for their roles in various diseases, including kidney disorders.
• The specific role of circHIPK3 in the pathogenesis of DN remains largely unexplored.

Purpose of the Study:

• To investigate the expression levels of circHIPK3 in a mouse model of DN.
• To elucidate the functional role of circHIPK3 in rat mesangial cells (MCs) under high glucose conditions.
• To explore the underlying molecular mechanism involving miR-185.

Main Methods:

• Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of circHIPK3, miR-185, and related genes (cyclin D1, PCNA, TGF-β1, Col. I, FN).
• Luciferase reporter assays were conducted to confirm the interaction between circHIPK3 and miR-185.
• Loss-of-function experiments (cell transfection) were performed to assess the impact of circHIPK3 and miR-185 silencing on MCs.

Main Results:

• Diabetic mice exhibited increased urinary albumin and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels.
• circHIPK3 expression was significantly upregulated in the renal tissues of DN mice and in MCs exposed to high glucose.
• Downregulation of circHIPK3 inhibited MC proliferation and reduced the expression of key genes involved in fibrosis and proliferation (cyclin D1, PCNA, TGF-β1, Col. I, FN).
• circHIPK3 was found to directly bind and sponge miR-185, and miR-185 inhibition reversed the effects of circHIPK3 knockdown.

Conclusions:

• circHIPK3 plays a pro-promotive role in the development of DN.
• The mechanism involves circHIPK3 sponging miR-185, leading to increased MC proliferation and extracellular matrix deposition.
• circHIPK3 represents a potential diagnostic biomarker and therapeutic target for diabetic nephropathy.