The role of TGF-β-activated kinase 1 in db/db mice and high glucose-induced macrophage.
Accumulating evidence reveals that inflammation plays a vital part in the development of diabetic nephropathy (DN), little information is available about the TGF-β-activated kinase 1 (TAK1) signal pathway activating inflammatory response in DN. We used bone marrow-derived macrophages (BMMs) and db/db mice to investigate the potential protective effects and mechanisms of TAK1 inhibitor (5Z-7-oxozeaenol) on diabetic kidney disease. The study showed that pretreatment with 5Z-7-oxozeaenol not only remarkably decreased high glucose (HG) stimulated excessive release of MCP-1 and TNF-α, but also significantly down-regulated ERK1/2, p38MAPK phosphorylation, and NF-κB activation in macrophages. In consistent, 5Z-7-oxozeaenol markedly reduced diabetes-induced albuminuria, histological changes, macrophage infiltration, and renal inflammatory cytokines expression and exerted its function through down-regulating ERK1/2, p38MAPK, NF-κB activation in the kidneys of db/db mice. Our findings may provide a novel direction to study the molecular mechanism and a perspective intervention to halt the progression of DN.
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, PR China.
Xingxin
X
Xu
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, PR China.
Zhe
Z
Fan
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, PR China.
Xiangming
X
Qi
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, PR China.
Yunxia
Y
Shao
Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230032, PR China. Electronic address: wuyonggui@medmail.com.cn.
Yonggui
Y
Wu
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics; D012118:Resorcinols / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7; D015025:Zearalenone / Q000008:administration & dosage
D018932:Chemokine CCL2; D007783:Lactones; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D054411:Receptors, Leptin; D012118:Resorcinols; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D015025:Zearalenone; C491768:Ccl2 protein, mouse
Diabetic nephropathy; Inflammation; MAPK; NF-κB; TAK1