Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

Autor: Chui-Wa Chow, Joseph Leung, Man-Fai Lam, Loretta Y.Y. Chan, Ai-Ing Lim, Kar-Neng Lai, Sydney C.W. Tang
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Time Factors
lcsh:Medicine
Angiotensin II - pharmacology - secretion
Apoptosis
urologic and male genital diseases
Kidney Tubules
Proximal
Renin-Angiotensin System
chemistry.chemical_compound
Transforming Growth Factor beta
11-beta-Hydroxysteroid Dehydrogenase Type 2
Receptor
Aldosterone
Cells
Cultured
Medicine(all)
Glomerulonephritis
IGA - enzymology - pathology
Angiotensin II
Glomerulonephritis
General Medicine
Kidney Tubules
Proximal - pathology
Up-Regulation
Crosstalk (biology)
Mesangial Cells
Female
medicine.medical_specialty
Oxidative phosphorylation
Biology
Receptor
Angiotensin
Type 2
General Biochemistry
Genetics and Molecular Biology
Nephropathy
Internal medicine
Renin–angiotensin system
medicine
Cytochrome P-450 CYP11B2
Humans
Epithelial Cells - drug effects - enzymology - pathology
Biochemistry
Genetics and Molecular Biology(all)
Research
lcsh:R
Epithelial Cells
Glomerulonephritis
IGA
medicine.disease
Immunoglobulin A
Oxidative Stress
Aldosterone - pharmacology
Endocrinology
Receptors
Mineralocorticoid
chemistry
Gene Expression Regulation
Zdroj: Journal of Translational Medicine, Vol 9, Iss 1, p 169 (2011)
Journal of Translational Medicine
Popis: BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN. METHODS: Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-beta synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS). RESULTS: Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-beta by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. CONCLUSIONS: Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.
published_or_final_version
Databáze: OpenAIRE
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