Lipotoxicity-Induced PRMT1 Exacerbates Mesangial Cell Apoptosis via Endoplasmic Reticulum Stress

Area of Science:

• Nephrology
• Cell Biology
• Molecular Biology

Background:

• Diabetic nephropathy (DN) progression is linked to lipotoxicity and mesangial cell apoptosis.
• Protein arginine methyltransferases (PRMTs) regulate cellular functions, with PRMT1 elevated in diabetic kidney conditions.
• The role of PRMTs in mesangial cells during diabetic nephropathy is not well understood.

Purpose of the Study:

• To investigate the role of PRMTs in lipotoxicity-induced mesangial cell apoptosis.
• To elucidate the signaling pathways involved in PRMT-mediated mesangial cell apoptosis under lipotoxic conditions.

Main Methods:

• Mesangial cells were treated with palmitate to induce lipotoxicity and endoplasmic reticulum (ER) stress.
• PRMT1 expression and activity were assessed following palmitate treatment.
• PRMT1 knockdown was performed to evaluate its effect on palmitate-induced apoptosis and ER stress.
• A mouse model of high fat diet-induced kidney damage was used, with PRMT1 haploinsufficient mice.

Main Results:

• Palmitate treatment induced mesangial cell apoptosis through PERK and ATF6-mediated ER stress.
• Palmitate increased PRMT1 expression and activity in mesangial cells.
• Knockdown of PRMT1 attenuated palmitate-induced ER stress and mesangial cell apoptosis.
• Glomerular apoptosis in mice fed a high-fat diet was reduced in PRMT1 haploinsufficient mice.

Conclusions:

• Lipotoxicity-induced PRMT1 expression promotes ER stress and mesangial cell apoptosis in diabetic nephropathy.
• Targeting PRMT1 offers a potential therapeutic strategy for preventing diabetic nephropathy exacerbation.