Long noncoding RNA SNHG5 promotes podocyte injury via the microRNA-26a-5p/TRPC6 pathway in diabetic nephropathy

Area of Science:

• Molecular Biology
• Genetics
• Nephrology

Background:

• Podocyte injury is a key feature of diabetic nephropathy (DN), but its underlying mechanisms remain unclear.
• Understanding these mechanisms is crucial for developing effective treatments for DN.
• Identifying specific molecular pathways involved in podocyte damage is a primary research goal.

Purpose of the Study:

• To investigate the role of long noncoding RNAs (lncRNAs) in podocyte injury in DN.
• To elucidate the regulatory pathway involving small nucleolar RNA host gene 5 (SNHG5), microRNA-26a-5p (miR-26a-5p), and transient receptor potential canonical type 6 (TRPC6) in DN.
• To evaluate the therapeutic potential of targeting the SNHG5/miR-26a-5p/TRPC6 pathway in DN.

Main Methods:

• Utilized db/db mice and immortalized mouse podocytes for experimental models.
• Employed high-throughput sequencing to identify differentially expressed lncRNAs in DN kidneys.
• Investigated the SNHG5/miR-26a-5p interaction using luciferase activity, RNA immunoprecipitation, and RNA pull-down assays.
• Assessed the effects of modulating SNHG5 and miR-26a-5p on podocyte injury in vitro and in vivo.

Main Results:

• Identified significantly increased TRPC6 expression and decreased miR-26a-5p in injured podocytes in DN.
• Demonstrated that miR-26a-5p directly targets the 3'-UTR of TRPC6, ameliorating podocyte injury.
• Confirmed upregulation of SNHG5 in DN kidneys and podocytes, which sponges miR-26a-5p.
• Showed that SNHG5 knockdown attenuated podocyte injury by increasing miR-26a-5p and decreasing TRPC6 expression, both in vitro and in vivo.

Conclusions:

• SNHG5 promotes podocyte injury in diabetic nephropathy through the miR-26a-5p/TRPC6 pathway.
• The SNHG5/miR-26a-5p/TRPC6 axis represents a novel mechanism contributing to DN pathogenesis.
• Targeting SNHG5 offers a potential therapeutic strategy for managing diabetic nephropathy.