An update: the role of Nephrin inside and outside the kidney

Li, XueZhu; He, John Cijiang

doi:10.1007/s11427-015-4844-1

Cited by 24 publications

(16 citation statements)

References 88 publications

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“…Podocytes play a vital role in the prevention of glomerular protein leakage during physiological and pathological processes through formation of slit diaphragm [37–40]. Clinical reports have demonstrated that smoking worsens the chronic kidney diseases, and enhances proteinuria [2–12].…”

Section: Discussionmentioning

confidence: 99%

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

et al. 2016

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BackgroundCigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury.MethodsTo determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS) generation (via DCFDA loading followed by fluorometric analysis), proliferation, and apoptosis (morphologic assays). We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury.ResultsHuman podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC) and TEMPOL (superoxide dismutase mimetic agent) inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte.ConclusionsNicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides insight into molecular mechanisms involved in smoking associated progression of chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

et al. 2016

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“…Other resident glomerular cells may have more significant roles in the activation of T cells around the glomeruli. Recent studies have indicated that podocytes from parietal epithelial cells were the predominant cellular components of crescents (Appel et al, 2009); these podocytes function as local professional antigen-presenting cells in the kidney (Goldwich et al, 2013) and may destroy its structure (Li et al, 2015). Further studies are required to determine the mechanisms of interaction between T cells and podocytes to elucidate the activation of CD4 + cells in the kidney in situ.…”

Section: Discussionmentioning

confidence: 99%

T cell infiltration is associated with kidney injury in patients with anti-glomerular basement membrane disease

Jia²,

Li³

et al. 2016

Sci. China Life Sci.

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“…This suggests the importance of nephrin in the process of glomerular filtration as a structural component of the slit diaphragm. Nephrin is exclusively expressed by podocytes but also may be expressed in brain, lymphoid tissue, heart, testis, placenta and β cells of the Langerhan's islets of the pancreas [6]. NPHS1 gene is located on chromosome 19 (19q13.1), organized in 29 exons [7].…”

Section: Nephrin -(Nph) Structure and Functionmentioning

confidence: 99%

Nephrin and Podocalyxin - New Podocyte Proteins for Early Detection of Secondary Nephropathies

et al. 2016

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In the last two decades a great progress was observed in understanding of podocytes, their specific structure and function identifying many specific podocyte proteins, such as nephrin and podocalyxin. Podocytes form the final barrier to plasma proteins leakage. Nephrin as a main component of the filtration diaphragm forms a physical barrier while podocalyxin as sialoglycoprotein forms an electrostatic barrier. Podocyte damage, i.e. podocytopathies and their loss through urine-podocyturia, are crucial in pathogenesis and progression of nephropathies with proteinuria as main clinical manifestation. In podocytopathies, nephrin and podocalyxin appear in the urine before proteinuria and microalbuminuria which were previously considered as earliest markers of nephropathies. Nephrinuria and podocalyxuria indicate damage of the podocytes on glomerular level and/or presence of apoptotic and necrotic podocytes in urine. These urinary markers are also important in early diagnosis of secondary nephropathies such as diabetic, lupus and hypertensive nephropathy as the most common causes of end-stage renal failure (ESRF). These markers are also important in the prediction of preeclampsia, which is the most common complication in pregnancy. In this review we elaborate in dept the main structural and functional features of podocytes and their specific proteins, nephrin and podocalyxin, summarizing the recent literature data on their importance in the early diagnosis of the most common secondary nephropathies.

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An update: the role of Nephrin inside and outside the kidney

Cited by 24 publications

References 88 publications

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

T cell infiltration is associated with kidney injury in patients with anti-glomerular basement membrane disease

Nephrin and Podocalyxin - New Podocyte Proteins for Early Detection of Secondary Nephropathies

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