Dataset Information

Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.

ABSTRACT: Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7519445 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Protective Role of Tangshen Formula on the Progression of Renal Damage in <i>db/db</i> Mice by TRPC6/Talin1 Pathway in Podocytes.

Wang Qian Q Tian Xuefei X Zhou Wei'e W Wang Yan Y Zhao Hailing H Li Jialin J Zhou Xuefeng X Zhang Haojun H Zhao Tingting T Li Ping P

Journal of diabetes research 20200916

Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of T ...[more]

PMID: 33015191

Similar Datasets

Project description:In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 μM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 μM) was significantly reduced, while the death rate in the medium dose group (25 μM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.

Project description:This study investigated the hypoglycemic and renal protective effects of scutellarin (SCU) in db/db mice and elucidated the underlying mechanisms. The oral administration of metformin hydrochloride (Met) at 120?mg/kg and SCU at 25, 50, and 100?mg/kg over an eight-week period had hypoglycemic effects, demonstrated by decreases in body weight, blood glucose, food and water intake, and glycated hemoglobin activity and by augmented insulin levels and pyruvate kinase activity in the serum of db/db mice. SCU alleviated dyslipidemia by decreasing the levels of triglycerides and total cholesterol and enhancing the levels of high-density lipoprotein cholesterol in the serum of db/db mice. SCU reversed the overexpression of mRNA of renal damage markers (receptor for advanced glycation end products, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1), macrophage marker CD11b, and T cell marker CD3 in kidney of db/db mice. Pathological examination confirmed that SCU improved the organ structures of hyperglycemia-damaged livers, kidneys, and pancreas islets. Antibody array assay and enzyme-linked immunosorbent assay were combined to screen and analyze the regulatory effects of SCU on inflammatory factors and oxidative enzymes. SCU exerted anti-inflammatory effects by inhibiting the levels of proinflammatory cytokines (glycogen synthase kinase, intercellular adhesion molecule 2, and interleukin 1? and 2) and promoting anti-inflammatory cytokines (interleukin 4). SCU decreased the reactive oxygen species and malondialdehyde concentrations and increased the activity levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) in serum and kidneys. Furthermore, SCU upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which in turn improved heme oxygenase 1 (HO-1), superoxide dismutase 1 and 2, and catalase expression levels in kidneys. The study showed that SCU has at least partial hypoglycemic and renal protective effects in db/db mice, and the mechanism is the modulation of the Nrf2/HO-1 signaling pathway.

Dataset Information

Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes.

Publications

Protective Role of Tangshen Formula on the Progression of Renal Damage in <i>db/db</i> Mice by TRPC6/Talin1 Pathway in Podocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets