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Spexin-based galanin receptor 2 agonist improves renal injury in mice with type 2 diabetes
차진주,박부연,윤성기,박혜진,유지애,기정연,차대룡,성재영,강영선 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1
The spexin-based GALR2 agonist (NS200) is a novel drug, which has shown antidepressant andanxiolytic action in a recent experimental study. In this study, we investigated the effects ofNS200 on renal injury in an animal model of type 2 diabetes. Eight-week-old diabetic db/dbmice were administered NS200 for 12 weeks. NS200 was intraperitoneally administered at adose of 1.0 mg/kg/day. Metabolic parameters and structural and molecular changes in thekidneys were compared among the three groups: non-diabetic db/m control, db/db mice, andNS200-treated db/db mice. In db/db mice, NS200 administration did not impact the bodyweight, food and water intake, urinary volume, fasting blood glucose level, or HbA1c levels. Insulin and glucose tolerance were also unaffected by NS200 treatment. However, NS200improved urinary albumin excretion and glomerulosclerosis in diabetic kidneys. Activation ofTGFβ1 and insulin signaling pathways, such as PI3 K /AKT/ERK, were inhibited by NS200. Inconclusion, a spexin-based GALR2 agonist attenuated diabetic nephropathy by alleviating renalfibrosis in mice with type 2 diabetes. Spexin-based GALR2 agonists have considerable potentialas novel treatment agents in diabetic nephropathy.
민혜숙,차진주,김기태,김정은,기정연,김현욱,이지은,한지영,정낙신,차대룡,강영선 대한의학회 2016 Journal of Korean medical science Vol.31 No.9
The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria.