Angpt2 Induces Mesangial Cell Apoptosis through the MicroRNA-33-5p-SOCS5 Loop in Diabetic Nephropathy

Area of Science:

• Nephrology
• Molecular Biology
• Endocrinology

Background:

• Diabetic nephropathy (DN) is a primary cause of end-stage renal disease, linked to mesangial cell (MC) loss and worsening kidney function.
• The angiopoietin (Angpt)/Tie system influences inflammation and angiogenesis; elevated Angpt2 correlates with poor renal outcomes in DN patients, but its role in MCs is unclear.

Purpose of the Study:

• To investigate the pathogenic role of Angpt2 in mesangial cells (MCs) in diabetic nephropathy (DN).
• To elucidate the molecular mechanisms underlying Angpt2-induced MC apoptosis and its association with kidney injury in DN.

Main Methods:

• Serum and urine samples from type 2 diabetes mellitus (DM) patients and db/db mice were analyzed for Angpt2 and miR-33-5p levels.
• MC apoptosis was induced by high glucose (HG) with or without Angpt2 treatment.
• Expression of miR-33-5p, SOCS5, JAK1, and STAT3 signaling pathways were assessed in MCs and kidney tissues.

Main Results:

• Serum Angpt2 levels were elevated in type 2 DM patients and db/db mice, correlating with albuminuria.
• Angpt2 synergistically induced MC apoptosis under high glucose conditions, a process regulated by miR-33-5p.
• Loss of miR-33-5p increased SOCS5, inhibiting JAK1/STAT3 signaling; elevated SOCS5 and decreased urinary miR-33-5p were observed in DN models and patients, correlating with albuminuria.

Conclusions:

• Angpt2 induces MC apoptosis in DN through the miR-33-5p-SOCS5 molecular pathway.
• Urinary miR-33-5p serves as a predictive biomarker for kidney injury in DN.
• These findings suggest potential therapeutic strategies targeting the Angpt2/miR-33-5p/SOCS5 axis for DN treatment.