Work

Acortatarin A inhibits high glucose-induced extracellular matrix production in mesangial cells

Year: 2013

Type: article

Abstract: BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Various treatment regimens and combinations of therapies provide only partial renoprotection. Therefore new approaches are needed to retard the progression of DN. The aim of the present study was to evaluate the role of a novel spiroalkaloid from Acorus tatarinowii named acortatarin A (AcorA) in inhibiting high glucose-induced extracellular matrix accumulation in mesangial cells (MCs). METHODS: The cytotoxity of AcorA on MCs was examined by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. The expression of fibronectin and collagen IV was examined by real time PCR and western blotting. The expression of p22(phox) and p47(phox) was detected by western blot. The interaction between p22(phox) and p47(phox) was examined by co-immunoprecipitation. The phosphorylation of p47(phox) was examined by immunoprecipitation. The phosphorylation of protein kinase C (PKC) α, PKCβ, phospholiase C gamma (PLCγ1), and the p85 subunit of PI3K was determined by Western blotting. RESULTS: AcorA significantly inhibited high glucose-induced activation of NADPH oxidase, a ROS-generating enzyme, by increasing phosphorylation of p47(phox) and enhancing interaction between p22(phox) and p47(phox). Preincubation of AcorA with MCs inhibited high glucose-induced collagen IV and fibronectin production in a dose-dependent manner. Moreover, AcorA attenuated high glucose enhanced phosphorylation of PKCα, PKCβ, PLCγ1, and the p85 subunit of PI3K. CONCLUSION: AcorA inhibits high glucose-induced extracellular matrix production via blocking NADPH oxidase activation.

Source: Chinese Medical Journal

DOI: 10.3760/cma.j.issn.0366-6999.20122445

Authors: Zhi-fang ZHAO, Li-li ZHOU, Xia CHEN, Yong-xian CHENG, Fan-fan HOU, Jing NIE

Institutions: Kunming Institute of Botany, Chinese Academy of Sciences, Nanfang Hospital, Southern Medical University

Language: English

Topic: Chronic Kidney Disease and Diabetes

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000