Angiotensin II type 1 receptor expression is increased via 12-lipoxygenase in high glucose-stimulated glomerular cells and type 2 diabetic glomeruli

Xu, Zhenhe; Miao, Lining; Cui, Yingchun; Jia, Yong; Yuan, Hang; Wu, Man

doi:10.1093/ndt/gfn703

Cited by 32 publications

(49 citation statements)

References 36 publications

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“…14 The molecular pathways contributing to podocyte injury in DN include, but are not limited to, high glucose and activation of the local renin-angiotensin system (RAS). 15 Angiotensin (Ang) II is one of the major effector molecules of the RAS and is the main target of established therapy for clinical DN. 15 Intraglomerular Ang II levels are increased in DN, 16 podocytes express Ang II receptors 17 and local glomerular RAS directly promotes filtration barrier injury.…”

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confidence: 99%

“…15 Angiotensin (Ang) II is one of the major effector molecules of the RAS and is the main target of established therapy for clinical DN. 15 Intraglomerular Ang II levels are increased in DN, 16 podocytes express Ang II receptors 17 and local glomerular RAS directly promotes filtration barrier injury. 15 Ang II promoted apoptosis of the cultured rat and mouse podocytes.…”

mentioning

confidence: 99%

“…15 Intraglomerular Ang II levels are increased in DN, 16 podocytes express Ang II receptors 17 and local glomerular RAS directly promotes filtration barrier injury. 15 Ang II promoted apoptosis of the cultured rat and mouse podocytes. [18][19][20] However, Ang II-induced apoptosis in human podocytes is not well characterized.…”

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confidence: 99%

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HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Sanchez-Niño

Sanz

Sánchez-López

et al. 2012

Laboratory Investigation

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Apoptosis is a driving force of diabetic end-organ damage, including diabetic nephropathy (DN). However, the mechanisms that modulate diabetes-induced cell death are not fully understood. Heat shock protein 27 (HSP27/HSPB1) is a cell stress protein that regulates apoptosis in extrarenal cells and is expressed by podocytes exposed to toxins causing nephrotic syndrome. We investigated the regulation of HSPB1 expression and its function in podocytes exposed to factors contributing to DN, such as high glucose and angiotensin (Ang) II. HSPB1 expression was assessed in renal biopsies from patients with DN, minimal change disease or focal segmental glomerulosclerosis (FSGS), in a rat model of diabetes induced by streptozotocin (STZ) and in Ang II-infused rats. The regulation of HSPB1 was studied in cultured human podocytes and the function of HSPB1 expressed in response to pathophysiologically relevant stimuli was explored by short interfering RNA knockdown. Total kidney HSPB1 mRNA and protein expression was increased in rats with STZ-induced diabetes and in rats infused with Ang II. Upregulation of HSPB1 protein was confirmed in isolated diabetic glomeruli. Immunohistochemistry showed increased glomerular expression of HSPB1 in both models and localized glomerular HSPB1 to podocytes. HSPB1 protein was increased in glomerular podocytes from patients with DN or FSGS. In cultured human podocytes HSPB1 mRNA and protein expression was upregulated by high glucose concentrations and Ang II. High glucose, but not Ang II, promoted podocyte apoptosis. HSPB1 short interfering RNA (siRNA) targeting increased apoptosis in a high-glucose milieu and sensitized to Ang II or TGFb1-induced apoptosis by promoting caspase activation. In conclusion, both high glucose and Ang II contribute to HSPB1 upregulation. HSPB1 upregulation allows podocytes to better withstand an adverse high-glucose or Ang II-rich environment, such as can be found in DN.

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HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Sanchez-Niño

Sanz

Sánchez-López

et al. 2012

Laboratory Investigation

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“…One of the renal hemodynamic effects of Ang II was assumed to be the increase in the products of the 12-lipoxygenase (12-LO) pathway (2). To support this early study (2), we demonstrated recently that the upregulation of AT1 is associated with the activated 12-LO pathway in the diabetic kidneys and the mesangial cells exposed to high levels of glucose (27,29).The 12-LO pathway derives several products to exert numerous physiological and pathological effects in the kidney. …”

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confidence: 80%

“…Both 12-LO and 12(S)-HETE were implicated in DN (10,22,27,29). However, how 12-LO induces renal dysfunction remains under investigation.…”

Section: One Of the 12-lo Products Is The Formation Of Oxidized Lipidmentioning

confidence: 99%

Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats

Guo

Miao

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats. Am J Physiol Endocrinol Metab 300: E708 -E716, 2011. First published February 1, 2011 doi:10.1152 doi:10. /ajpendo.00624.2010 was implicated in the development of diabetic nephropathy (DN), in which the proteinuria was thought to be associated with a decreased expression of glomerular P-cadherin. Therefore, we investigated the role of 12-LO in the glomerular P-cadherin expression in type 2 diabetic rats according to the glomerular sizes. Rats fed with high-fat diet for 6 wk were treated with low-dose streptozotocin. Once diabetes onset, diabetic rats were treated with 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) for 8 wk. Then glomeruli were isolated from diabetic and control rats with a sieving method. RT-PCR, Western blotting, and immunofluorescent staining were used for mRNA and protein expressions of P-cadherin and angiotensin II (Ang II) type 1 receptor (AT1). We found that CDC did not affect the glucose levels but completely attenuated diabetic increases in glomerular volume and proteinuria. Diabetes significantly decreased the P-cadherin mRNA and protein expressions and increased the AT1 mRNA and protein expressions in the glomeruli. These changes were significantly prevented by CDC and recaptured by direct infusion of 12-LO product [12(S)-HETE] to normal rats for 7 days. The decreased P-cadherin expression was similar between large and small glomeruli, but the increased AT1 expression was significantly higher in the large than in the small glomeruli from diabetic and 12(S)-HETE-treated rats. Direct infusion of normal rats with Ang II for 14 days also significantly decreased the glomerular P-cadherin expression. These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular Pcadherin expression. diabetic nephropathy; slit diaphragm; high-fat diet; 12(S)-hydroxyeicosatetraenoic acid; P-cadherin inhibitor GLOMERULAR HYPERTROPHY AND PROTEINURIA are hallmarks of the early diabetic nephropathy (DN) and can be induced by hyperglycemia and several growth factors, such as angiotensin II (Ang II), via their specific receptors (19). There are two Ang II plasma receptors, referred to as Ang II type 1 receptor (AT1) and type 2 receptor subtypes (6). Most of the known effects of Ang II in the adult tissues are attributable to AT1 intracellular signaling (6,20,25). Thus the expression of AT1 is important for the biological effect of Ang II. A number of clinical and experimental studies have demonstrated that AT1 antagonists reduce the damage of renal tissue and decrease proteinuria (3,5,26). One of the renal hemodynamic effects of Ang II was assumed to be the increase in the products of the 12-lipoxygenase (12-LO) pathway (2). To support this early study (2), we demonstrated recently that the upregulation of AT1 is associated with the activated 12-LO pathway in th...

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Flow cytometric analysis of circulating microparticles in plasma

2010

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Microparticles, which include exosomes, micro-vesicles, apoptotic bodies and apoptotic microparticles, are small (0.05 -3 lm in diameter), membranous vesicles that can contain DNA, RNA, miRNA, intracellular proteins and express extracellular surface markers from the parental cells. They can be secreted from intracellular multivesicular bodies or released from the surface of blebbing membranes. Circulating microparticles are abundant in the plasma of normal individuals and can be derived from circulating blood cells such as platelets, red blood cells and leukocytes as well as from tissue sources, such as endothelial and placental tissues. Elevated levels of microparticles are associated with various diseases such as thrombosis (platelet microparticles), congestive heart failure (endothelial microparticles), breast cancer patients (leukocyte microparticles) and women with preeclampsia (syncytiotrophoblast microparticles). Although microparticles can be detected by microscopy, enzyme-linked immunoassays and functional assays, flow cytometry is the preferred method because of the ability to quantitate (fluorescent bead-or flow rate-based method) and because of polychromatic capabilities. However, standardization of pre-analytical and analytical modus operandi for isolating, enumerating and fluorescent labeling of microparticles remains a challenge. The primary focus of this article is to review the preliminary steps required to optimally study circulating in vivo microparticles which include: 1) centrifugation speed used, 2) quantitation of microparticles before antibody labeling, 3) levels of fluorescence intensity of antibody-labeled microparticles, 4) polychromatic flow cytometric analysis of microparticle sub-populations and 5) use of polyclonal antibodies designed for Western blotting for flow cytometry. These studies determine a roadmap to develop microparticles as biomarkers for a variety of conditions. ' 2010 International Society for Advancement of Cytometry Key terms quantitation of plasma microparticles; polychromatic flow cytometric analysis; Western blotting polyclonal antibodies OVER the years, the quiet waters of flow cytometric analysis of circulating microparticles (MPs) have given way to a deluge of original articles, technical briefs, and critical reviews. However, given the vast scope of work about circulating MPs, it is not possible to cover all the literature. Instead, this review focuses on flow cytometric analysis and applications of fetal-derived MPs. Although other cell-derived MPs such as platelet MPs (PMPs), endothelial MPs (EMPs), and leukocyte MP (LMPs) are not a focus of this review, many of the same principles apply.

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Angiotensin II type 1 receptor expression is increased via 12-lipoxygenase in high glucose-stimulated glomerular cells and type 2 diabetic glomeruli

Abstract: These results indicate that AT1 expression is enhanced, at least in part, by 12-LO in the type 2 diabetic glomeruli, and 12-LO inhibition can ameliorate DN progression through downregulation of AT1 expression.

Cited by 32 publications

References 36 publications

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats

Flow cytometric analysis of circulating microparticles in plasma

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