lc15-0444 and Fibrosis

lc15-0444 has been researched along with Fibrosis* in 3 studies

Other Studies

3 other study(ies) available for lc15-0444 and Fibrosis

ArticleYear
Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome.
    Diabetes & metabolism journal, 2019, Volume: 43, Issue:6

    The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.. We examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and. Immunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with the. The present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.

    Topics: Administration, Oral; Animals; Cell Line; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Down-Regulation; Fibrosis; Humans; Inflammasomes; Inflammation; Kidney Tubules, Proximal; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Piperidones; Protective Agents; Pyrimidines; Signal Transduction; Transforming Growth Factor beta; Ureteral Obstruction

2019
Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice.
    Canadian journal of physiology and pharmacology, 2017, Volume: 95, Issue:2

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

    Topics: Adipocytes; Animals; Diet, Western; Fatty Liver; Fibrosis; Hypercholesterolemia; Hypertrophy; Inflammation; Insulin Resistance; Liver; Male; Metabolic Syndrome; Mice; Piperidones; Pyrimidines; Subcutaneous Fat; Uncoupling Protein 1; Weight Gain

2017
Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction.
    Laboratory investigation; a journal of technical methods and pathology, 2014, Volume: 94, Issue:6

    Dipeptidyl peptidase IV (DPPIV) is an exopeptidase that modulates the function of several substrates, among which insulin-releasing incretin hormones are the most well known. DPPIV also modulate substrates involved in inflammation, cell migration, and cell differentiation. Although DPPIV is highly expressed in proximal renal tubular cells, the role of DPPIV inhibition in renal disease is not fully understood. For this reason, we investigated the effects of LC15-0444, a DPPIV inhibitor, on renal function in a mouse model of renal fibrosis. Eight-week-old C57/BL6 mice were subjected to unilateral ureteral obstruction (UUO) and were treated with LC15-0444 (a DPPIV inhibitor) at a dose of 150 mg/kg per day in food or vehicle for 14 days. DPPIV activity was significantly increased in obstructed kidneys, and reduced after treatment with LC15-0444. Administration of LC15-0444 resulted in a significant decrease in albuminuria, urinary excretion of 8-isoprostane, and renal fibrosis. DPPIV inhibition also substantially decreased the synthesis of several proinflammatory and profibrotic molecules, as well as the infiltration of macrophages. UUO significantly increased, and LC15-0444 markedly suppressed, levels of phosphorylated Smad2/3, TGFβ1, toll-like receptor 4, high-mobility group box-1, NADPH oxidase 4, and NF-κB. These results suggest that activation of DPPIV in the kidney has a role in the progression of renal disease and that targeted therapy inhibiting DPPIV may prove to be a useful new approach in the management of progressive renal disease, independent of mechanisms mediated by glucagon-like peptide-1.

    Topics: Animals; Cytokines; Dinoprost; Dipeptidyl-Peptidase IV Inhibitors; Fibrosis; Kidney; Kidney Diseases; Mice; Mice, Inbred C57BL; Oxidative Stress; Piperidones; Proteinuria; Pyrimidines; Statistics, Nonparametric; Ureteral Obstruction

2014