Lack of α8-integrin aggravates podocyte injury in experimental diabetic nephropathy

Hartner, Andrea; Cordasic, Nada; Menendez-Castro, Carlos; Volkert, Gudrun; Yabu, Julie M.; Kupraszewicz-Hutzler, Miroslava; Rascher, Wolfgang; Hilgers, Karl F.

doi:10.1152/ajprenal.00058.2010

Cited by 23 publications

(17 citation statements)

References 41 publications

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“…Hypercholesterolemia is a risk factor for renal damage [3, 4], although Apoe -deficient mice without an atherogenic diet do not commonly develop overt renal pathologies [5]. We, therefore, crossed Apoe -deficient mice with mice which had a deletion of the Itga8 (alpha8 integrin) gene, which have reduced nephron numbers and are prone to develop renal disease when challenged [6]. Alpha8 integrin is a matrix receptor mainly found on mesenchymal cells like vascular smooth muscle cells and renal mesangial cells [7].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

et al. 2017

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Background Apoe-deficient (Apoe −/−) mice develop progressive atherosclerotic lesions with age but no severe renal pathology in the absence of additional challenges. We recently described accelerated atherosclerosis as well as marked renal injury in Apoe −/− mice deficient in the mesenchymal integrin chain Itga8 (Itga8 −/−). Here, we used this Apoe −/−, Itga8 −/− mouse model to investigate the sex differences in the development of atherosclerosis and concomitant renal injury. We hypothesized that aging female mice are protected from vascular and renal damage in this mouse model.Methods Apoe −/− mice were backcrossed with Itga8 −/− mice. Mice were kept on a normal diet. At the age of 12 months, the aortae and kidneys of male and female Apoe −/− Itga8 +/+ mice or Apoe −/− Itga8 −/− mice were studied. En face preparations of the aorta were stained with Sudan IV (lipid deposition) or von Kossa (calcification). In kidney tissue, immunostaining for collagen IV, CD3, F4/80, and PCNA and real-time PCR analyses for Il6, Vegfa, Col1a1 (collagen I), and Ssp1 (secreted phosphoprotein 1, synonym osteopontin) as well as ER stress markers were performed.ResultsWhen compared to male mice, Apoe −/− Itga8 +/+ female mice had a lower body weight, equal serum cholesterol levels, and lower triglyceride levels. However, female mice had increased aortic lipid deposition and more aortic calcifications than males. Male Apoe −/− mice with the additional deficiency of Itga8 developed increased serum urea, glomerulosclerosis, renal immune cell infiltration, and reduced glomerular cell proliferation. In females of the same genotype, these renal changes were less pronounced and were accompanied by lower expression of interleukin-6 and collagen I, while osteopontin expression was higher and markers of ER stress were not different.ConclusionsIn this model of atherosclerosis, the female sex is a risk factor to develop more severe atherosclerotic lesions, even though serum fat levels are higher in males. In contrast, female mice are protected from renal damage, which is accompanied by attenuated inflammation and matrix deposition. Thus, sex affects vascular and renal injury in a differential manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0141-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

et al. 2017

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“…There is still a lack of specific and effective treatment, although angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been proscribed to slow the progression of DN (Mandal and Hiebert, 2008). Increased albumin excretion is an important manifestation of renal injury in DN (Hartner et al, 2010). The severity of albuminuria is positively related to the duration and level of high blood glucose (Ninomiya et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy

Zhang¹,

Liu²,

Xiong

et al. 2012

Journal of Ethnopharmacology

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“…In this context, integrin a8-null mice present with abnormalities of the mesangium characterized by hypercellularity and altered glomerular capillaries, most likely due to impaired ability to protect the glomerulus from mechanical stress, including hypertension. [36][37][38] In addition, there is evidence that a polymorphism within the promoter of the integrin a8 subunit regulates the progression of polycystic kidney disease. 39 Altogether these findings suggest that mutations or loss of function of the a8 subunit could render humans more susceptible to stress-induced glomerular damage or polycystic kidney disease.…”

Section: The Rgd-binding Integrinsmentioning

confidence: 99%

Integrins in Kidney Disease

Pozzi

Zent²

2013

Journal of the American Society of Nephrology

107

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A major hallmark of chronic kidney injury is fibrosis, which is characterized by increased accumulation of extracellular matrix components that replace the damaged tissue. Normally, the synthesis and degradation of extracellular matrix components are finely regulated; however, when matrix replacement goes unchecked, there is unwanted and irreversible tissue scarring with consequent organ damage, organ failure, and, in certain cases, death. Many factors, including cell-matrix interactions, play a role in the development of renal fibrosis. Cell-matrix interactions are made possible by integrins, a family of transmembrane receptors that, upon binding to the extracellular matrix, activate intracellular signaling. Thus, they control various cell functions, including survival, proliferation, migration, and matrix homeostasis. Genetic mutations in humans and the development of animal models lacking integrins in selective parts of the kidney have improved our understanding of molecular mechanisms and pathways controlling matrix remodeling in kidney disease. Here we outline the major integrins involved in kidney disease and some of the major molecular mechanisms whereby integrins contribute to kidney fibrosis.

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Lack of α8-integrin aggravates podocyte injury in experimental diabetic nephropathy

Cited by 23 publications

References 41 publications

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

Sex differences in the development of vascular and renal lesions in mice with a simultaneous deficiency of Apoe and the integrin chain Itga8

Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy

Integrins in Kidney Disease

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