A deletion in the N-terminal polymerizing domain of laminin β2 is a new mouse model of chronic nephrotic syndrome

Abstract Nephrotic syndrome (NS) is a renal disorder that is characterized by massive proteinuria, hypoalbuminemia and edema. One of the main causes of NS is focal segmental glomerulosclerosis (FSGS), which has extremely poor prognosis. Although steroids and immunosuppressants are the first line of treatment, some FSGS cases are refractory, prompting the need to find new therapeutic strategies. We have previously demonstrated that an optimized combination treatment of mild electrical stimulation (MES) and heat shock (HS) has several biological benefits including the amelioration of the pathologies of the genetic renal disorder Alport syndrome. Here, we investigated the effect of MES + HS on adriamycin (ADR)-induced NS mouse model. MES + HS suppressed proteinuria and glomerulosclerosis induced by ADR. The expressions of pro-inflammatory cytokines and pro-fibrotic genes were also significantly downregulated by MES + HS. MES + HS decreased the expression level of cleaved caspase-3 and the number of TUNEL-positive cells, indicating that MES + HS exerted anti-apoptotic effect. Moreover, MES + HS activated the Akt signaling and induced the phosphorylation and inhibition of the apoptotic molecule BAD. In in vitro experiment, the Akt inhibitor abolished the MES + HS-induced Akt-BAD signaling and anti-apoptotic effect in ADR-treated cells. Collectively, our study suggested that MES + HS modulates ADR-induced pathologies and has renoprotective effect against ADR-induced NS via regulation of Akt-BAD axis.

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Plasminogen deficiency does not prevent sodium retention in a genetic mouse model of experimental nephrotic syndrome

Acta Physiologica ◽

10.1111/apha.13512 ◽

2020 ◽

Vol 231 (1) ◽

Author(s):

Mengyun Xiao ◽

Bernhard N. Bohnert ◽

Hande Aypek ◽

Oliver Kretz ◽

Florian Grahammer ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mouse Model ◽

Sodium Retention ◽

Genetic Mouse Model ◽

Plasminogen Deficiency

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A Humanized Mouse Model of Idiopathic Nephrotic Syndrome Suggests a Pathogenic Role for Immature Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.2006121346 ◽

2007 ◽

Vol 18 (10) ◽

pp. 2732-2739 ◽

Cited By ~ 57

Author(s):

Anne-Laure Sellier-Leclerc ◽

Arnaud Duval ◽

Stéphanie Riveron ◽

Marie-Alice Macher ◽

Georges Deschenes ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mouse Model ◽

Idiopathic Nephrotic Syndrome ◽

Humanized Mouse ◽

Pathogenic Role ◽

Humanized Mouse Model ◽

Immature Cells

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An inducible mouse model of podocin-mutation-related nephrotic syndrome

PLoS ONE ◽

10.1371/journal.pone.0186574 ◽

2017 ◽

Vol 12 (10) ◽

pp. e0186574 ◽

Cited By ~ 8

Author(s):

Mansoureh Tabatabaeifar ◽

Tanja Wlodkowski ◽

Ivana Simic ◽

Helga Denc ◽

Geraldine Mollet ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mouse Model

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Ferulic Acid, anAngelica sinensis-Derived Polyphenol, Slows the Progression of Membranous Nephropathy in a Mouse Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/161235 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Chao-Wen Cheng ◽

Wen-Liang Chang ◽

Li-Cheng Chang ◽

Chia-Chao Wu ◽

Yuh-Feng Lin ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Mouse Model ◽

Ferulic Acid ◽

Membranous Nephropathy ◽

Angelica Sinensis ◽

Therapeutic Effects ◽

Th2 Response ◽

Adequate Treatment ◽

Oxidative Stresses ◽

Antiangiogenic Factors

Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome but lacks adequate treatment. Different extracts ofAngelica sinensis(AS) and one of its active compounds, ferulic acid (FA), were used to evaluate the therapeutic effects in a MN mouse model. The MN model was grouped into three subgroups: no treatment (N-T), treatment at induction of MN (Pre-T), and treatment after full-blown MN (Post-T). The results showed that the methanol (ME) layer of AS extract exhibited a therapeutic effect on MN-induced proteinuria. The ME layer-enriched compound, FA, improved the hypoalbuminemia, hyperlipidemia, and proteinuria in both Pre-T and Post-T groups. Ferulic acid also reduced the formation of oxidative protein products and increased the synthesis of antioxidant enzymes in groups Pre-T and Post-T. Regarding angiogenesis factors, the antiangiogenic factors in renal glomeruli were increased in group N-T, but, after FA treatment, only one of the antiangiogenic factors, thrombospondin-1, showed a significant decrease. Furthermore, the expression of Th2 predominant showed significant decrease in both Pre-T and Post-T groups when compared to that of N-T group. In summary, FA retarded the progression of MN, and the mechanisms involved the regulation of oxidative stresses, angiogenic and antiangiogenic factors, and attenuation of Th2 response.

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Hereditary Nephrotic Syndrome with Progression to Renal Failure in a Mouse Model (ICGN Strain): Clinical Study

Nephron ◽

10.1159/000188264 ◽

1994 ◽

Vol 68 (2) ◽

pp. 239-244 ◽

Cited By ~ 26

Author(s):

Atsuo Ogura ◽

Toshihiko Asano ◽

Osamu Suzuki ◽

Yoshie Yamamoto ◽

Yoko Noguchi ◽

...

Keyword(s):

Renal Failure ◽

Nephrotic Syndrome ◽

Clinical Study ◽

Mouse Model

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Faculty Opinions recommendation of A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.721439815.793515383 ◽

2016 ◽

Author(s):

Moin Saleem

Keyword(s):

Nephrotic Syndrome ◽

Mouse Model ◽

Idiopathic Nephrotic Syndrome ◽

Humanized Mouse ◽

Pathogenic Role ◽

Humanized Mouse Model ◽

Immature Cells

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Mutations in LAMB2 Are Associated With Albuminuria and Optic Nerve Hypoplasia With Hypopituitarism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz216 ◽

2019 ◽

Vol 105 (3) ◽

pp. 595-599

Author(s):

Mona Tahoun ◽

Jennifer C Chandler ◽

Emma Ashton ◽

Scott Haston ◽

Athia Hannan ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Optic Nerve ◽

Basement Membrane ◽

Anterior Pituitary ◽

Congenital Nephrotic Syndrome ◽

Optic Nerve Hypoplasia ◽

Hormone Deficiency ◽

Compound Heterozygous ◽

Macroscopic Hematuria ◽

Laminin Β2

Abstract Context Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome). Case description This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2–/– mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland. Conclusion We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2.

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