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 μmol/L NAC). After 24 h, the expression of ROS, NLRP3, caspase-1, procaspase-1, IL-1β, and pro-IL-1β was detected by western-blot, RT-PCR, and immunofluorescence. After 48 h, the expression of TGF-β1 and FN was detected by RT-PCR and ELISA. Results. Compared with normal glucose group, the expression of ROS, NLRP3, caspase-1, IL-1β, TGF-β1, and FN increased in high glucose group (P < 0.05), but it decreased after the treatment of maresin 1 in different concentrations. On the contrary, the expression of procaspase-1 and pro-IL-1β protein was restrained by high glucose and enhanced by maresin 1 in a dose-dependent manner (P < 0.05). Conclusion. Maresin 1 can inhibit NLRP3 inflammasome, TGF-β1, and FN in GMCs; it may have protective effect on DN by mitigating the inflammation and early fibrosis.

Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

“…However, we did not find macrophages in renal cortex of DN mice model. 29 Our study showed that in renal biopsy samples of DN patients and renal cortex of DN mice, expression levels of TGF-β1 and other inflammatory factors increased as ChemR23 was elevated. It was suggested that chronic inflammation played a crucial role in the occurrence and development of DN.…”

“…In DN, elevated expression of TGF-β1 was often accompanied by gradual fibrosis and finally led to renal failure. 29 Our study showed that in renal biopsy samples of DN patients and renal cortex of DN mice, expression levels of TGF-β1 and other inflammatory factors increased as ChemR23 was elevated.…”

Maresin 1 attenuates mitochondrial dysfunction through the ALX/cAMP/ROS pathway in the cecal ligation and puncture mouse model and sepsis patients

“…Finally, previous studies showed that MaR1 decreased ROS levels during lung I/R Injury [40]. The expression of ROS increased in the presence of high glucose group, but it decreased after the treatment with MaR1 at different concentrations [41]. Another study showed that ROS levels were decreased by treatment of MaR1 in Carbon Tetrachloride-Induced Liver Injury in Mice [42].…”

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

“…MaR-1 is effective in controlling inflammation in periodontal infections with unresolved inflammation and leukocyte-mediated tissue destruction (108), and restoring the reparative function of nonhealing diabetic wounds impaired the macrophages (109). MaR-1 has also been tested in the treatment of diabetic nephropathy by inhibiting nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing-3 and controls the inflammation rate in renal failure (110).…”