Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis

Area of Science:

• Cell Biology
• Molecular Biology
• Nephrology

Background:

• Diabetic nephropathy (DN) is a severe diabetes complication characterized by sterile inflammation.
• Pyroptosis, a pro-inflammatory cell death, is increasingly implicated in DN pathogenesis.
• The precise molecular drivers of pyroptosis in DN remain largely unelucidated.

Purpose of the Study:

• To investigate the role of long non-coding RNA NEAT1 in pyroptosis during diabetic nephropathy.
• To elucidate the molecular pathway involving NEAT1, miR-34c, and NLRP3 in DN-induced pyroptosis.

Main Methods:

• Established rat models of diabetic nephropathy using streptozotocin.
• Utilized high glucose conditions to mimic DN in cultured glomerular mesangial cells.
• Quantified gene and protein expression via qPCR and Western blot; assessed cell viability and pyroptosis using MTT assay and flow cytometry.
• Confirmed molecular interactions using luciferase reporter assays.

Main Results:

• Upregulation of NEAT1 correlated with increased pyroptosis in DN models.
• NEAT1 influenced pyroptosis by regulating NLRP3, caspase-1, and interleukin-1β expression via miR-34c.
• Inhibition of miR-34c or overexpression of NLRP3 counteracted pyroptosis and inflammation induced by NEAT1 knockdown in vitro.

Conclusions:

• NEAT1 and its target miR-34c regulate pyroptosis in diabetic nephropathy by modulating NLRP3.
• These findings offer novel insights into the molecular mechanisms of pyroptosis in DN pathogenesis.