Nephrin in human lymphoid tissues

Åström, Eva; Rinta-Valkama, Johanna; Gylling, M; Ahola, Heikki; Miettinen, Aaro; Timonen, Tuomo; Holthöfer, Harry

doi:10.1007/s00018-005-5498-0

Cited by 20 publications

(11 citation statements)

References 35 publications

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“…Consistent with previous reports, we also identified the 160-kDa nephrin band in extrarenal organs: heart, spleen, pancreas, and brain (Supplemental Figure 1E). 7,34,35 The exclusive presence of the 180-kD band in the kidney lysate has been described previously. 35 Because DOX does not cross the blood-brain barrier, GFP and nephrin expressions did not different between mice with and without induction.…”

Section: Murine Model Of Inducible Nephrin Knockdownmentioning

confidence: 99%

“…7,34,35 The exclusive presence of the 180-kD band in the kidney lysate has been described previously. 35 Because DOX does not cross the blood-brain barrier, GFP and nephrin expressions did not different between mice with and without induction. Histologic features of the myocardium did not appear to be different between sh3703 and Luci.1309 mice (Supplemental Figure 1F).…”

Section: Murine Model Of Inducible Nephrin Knockdownmentioning

confidence: 99%

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Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Chuang

D’Agati

et al. 2015

Journal of the American Society of Nephrology

105

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Nephrin is required during kidney development for the maturation of podocytes and formation of the slit diaphragm junctional complex. Because nephrin expression is downregulated in acquired glomerular diseases, nephrin deficiency is considered a pathologic feature of glomerular injury. However, whether nephrin deficiency exacerbates glomerular injury in glomerular diseases has not been experimentally confirmed. Here, we generated mice with inducible RNA interference-mediated nephrin knockdown. Short-term nephrin knockdown (6 weeks), starting after the completion of kidney development at 5 weeks of age, did not affect glomerular structure or function. In contrast, mice with long-term nephrin knockdown (20 weeks) developed mild proteinuria, foot process effacement, filtration slit narrowing, mesangial hypercellularity and sclerosis, glomerular basement membrane thickening, subendothelial zone widening, and podocyte apoptosis. When subjected to an acquired glomerular insult induced by unilateral nephrectomy or doxorubicin, mice with short-term nephrin knockdown developed more severe glomerular injury compared with mice without nephrin knockdown. Additionally, nephrin-knockdown mice developed more exaggerated glomerular enlargement when subjected to unilateral nephrectomy and more podocyte apoptosis and depletion after doxorubicin challenge. AKT phosphorylation, which is a slit diaphragm-mediated and nephrin-dependent pathway in the podocyte, was markedly reduced in mice with long-term or short-term nephrin knockdown challenged with uninephrectomy or doxorubicin. Taken together, our data establish that under the basal condition and in acquired glomerular diseases, nephrin is required to maintain slit diaphragm integrity and slit diaphragm-mediated signaling to preserve glomerular function and podocyte viability in adult mice.

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Section: Murine Model Of Inducible Nephrin Knockdownmentioning

confidence: 99%

Section: Murine Model Of Inducible Nephrin Knockdownmentioning

confidence: 99%

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Chuang

D’Agati

et al. 2015

Journal of the American Society of Nephrology

105

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“…In contrast, cadherin-11 expression increases during the formation of multinucleated syncytia, and it promotes the morphological and functional differentiation of human CTB cells (Getsios & MacCalman 2003). The expression of nephrin has been found in the kidney, pancreas, brain, and lymphoid tissues (Putaala et al 2001, Astrom et al 2006. Verma et al (2006) have observed that mutation or deletion of nephrin protein in the slit diaphragm in the kidney leads to a defect in podocyte foot process morphogenesis, and that proteinuria is the clinical symptom.…”

Section: Discussionmentioning

confidence: 99%

Involvement of nephrin in human placental trophoblast syncytialization

Li¹,

Zheng²,

Wang³

et al. 2015

Reproduction

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The placenta has numerous functions, such as transporting oxygen and nutrients and building the immune tolerance of the fetus. Cell fusion is an essential process for placental development and maturation. In human placental development, mononucleated cytotrophoblast (CTB) cells can fuse to form a multinucleated syncytiotrophoblast (STB), which is the outermost layer of the placenta. Nephrin is a transmembrane protein that belongs to the Ig superfamily. Previous studies have shown that nephrin contributes to the fusion of myoblasts into myotubes in zebrafish and mice, presenting a functional conservation with its Drosophila ortholog sticks and stones. However, whether nephrin is involved in trophoblast syncytialization remains unclear. In this study, we report that nephrin was localized predominantly in the CTB cells and STB of human placenta villi from first trimester to term pregnancy. Using a spontaneous fusion model of primary CTB cells, the expression of nephrin was found to be increased during trophoblast cell fusion. Moreover, the spontaneous syncytialization and the expression of syncytin 2, connexin 43, and human chorionic gonadotropin beta were significantly inhibited by nephrin-specific siRNAs. The above results demonstrate that nephrin plays an important role in trophoblast syncytialization.

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“…It becomes more and more evident that, outside the nervous system, glutamate signalling is utilized not only by podocytes but also by other cells, such as lymphocytes, testis cells and pancreatic β cells, all of them requiring precise modulation of specific functions. Not surprisingly, nephrin expression has been selectively found in the very same locations 52–55, and it will be interesting to investigate its molecular interactions also in these systems.…”

Section: Discussionmentioning

confidence: 99%

Nephrin expression in adult rodent central nervous system and its interaction with glutamate receptors

Li¹,

Armelloni²,

Ikehata³

et al. 2011

The Journal of Pathology

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Nephrin is an immunoglobulin-like adhesion molecule first discovered as a major component of the podocyte slit diaphragm, where its integrity is essential to the function of the glomerular filtration barrier. Outside the kidney, nephrin has been shown in other restricted locations, most notably in the central nervous system (CNS) of embryonic and newborn rodents. With the aim of better characterizing nephrin expression and its role in the CNS of adult rodents, we studied its expression pattern and possible binding partners in CNS tissues and cultured neuronal cells and compared these data to those obtained in control renal tissues and podocyte cell cultures. Our results show that, besides a number of locations already found in embryos and newborns, endogenous nephrin in adult rodent CNS extends to the pons and corpus callosum and is expressed by granule cells and Purkinje cells of the cerebellum, with a characteristic alternating expression pattern. In primary neuronal cells we find nephrin expression close to synaptic proteins and demonstrate that nephrin co-immunoprecipitates with Fyn kinase, glutamate receptors and the scaffolding molecule PSD95, an assembly that is reminiscent of those made by synaptic adhesion molecules. This role seems to be confirmed by our findings of impaired maturation and reduced glutamate exocytosis occurring in Neuro2A cells upon nephrin silencing. Of note, we disclose that the very same nephrin interactions occur in renal glomeruli and cultured podocytes, supporting our hypothesis that podocytes organize and use similar molecular intercellular signalling modules to those used by neuronal cells.

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Nephrin in human lymphoid tissues

Cited by 20 publications

References 35 publications

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Involvement of nephrin in human placental trophoblast syncytialization

Nephrin expression in adult rodent central nervous system and its interaction with glutamate receptors

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