Maresin 1 Mitigates High Glucose-Induced Mouse Glomerular Mesangial Cell Injury by Inhibiting Inflammation and Fibrosis

Abstract

Background . Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim . We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods . We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μ mol/L NAC). After 24 h, the expression of ROS, NLRP3, caspase-1, procaspase-1, IL-1 β , and pro-IL-1 β was detected by western-blot, RT-PCR, and immunofluorescence. After 48 h, the expression of TGF- β 1 and FN was detected by RT-PCR and ELISA. Results . Compared with normal glucose group, the expression of ROS, NLRP3, caspase-1, IL-1 β , TGF- β 1, and FN increased in high glucose group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>), but it decreased after the treatment of maresin 1 in different concentrations. On the contrary, the expression of procaspase-1 and pro-IL-1 β protein was restrained by high glucose and enhanced by maresin 1 in a dose-dependent manner (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). Conclusion . Maresin 1 can inhibit NLRP3 inflammasome, TGF- β 1, and FN in GMCs; it may have protective effect on DN by mitigating the inflammation and early fibrosis.