CD2AP, Dendrin, and Cathepsin L in the Kidney

Sever, Sanja; Reiser, Jochen

doi:10.1016/j.ajpath.2015.06.022

Cited by 8 publications

(6 citation statements)

References 7 publications

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“…16 It can combine with PC2 and disrupt PC1-PC2 combination to cause cystogenesis. 17 This study had four limitations. First, the regulation of macrophage polarization is not limited to l-LAarginine-polyamine pathway.…”

Section: Discussionmentioning

confidence: 94%

Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1−/− Mice by Regulating Macrophage M2 Polarization

et al. 2023

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Adult autosomal dominant polycystic kidney disease (ADPKD) has been shown to be related as a "third hit" to the occurrence of acute or chronic kidney injury. Here, we examined whether dehydration, as a common kidney risk factor, could cause cystogenesis in chronic-onset Pkd1 −/− mice by regulating macrophage activation. First, we con rmed that dehydration accelerated cytogenesis in Pkd1 −/− mice and that macrophages in ltrated the kidney tissues even earlier than macroscopic cyst formation. Then, microarray analysis suggested that glycolysis pathway may be involved in macrophage activation in Pkd1 −/− kidneys under conditions of dehydration. Further, we con rmed glycolysis pathway was activated and lactic acid (L-LA) was overproduced in the Pkd1 −/− kidney under conditions of dehydration. We have already proved that L-LA strongly stimulated M2 macrophage polarization and overproduction of polyamine in macrophage in vitro; and in the present study, we further discovered that M2 polarizationinduced polyamine production shortened the primary cilia length by disrupting the PC1/PC2 complex. Finally, the activation of L-LA-arginase 1-polyamine pathway contributed to cystogenesis and progressive cyst growth in Pkd1 −/− mice recurrently exposed to dehydration.

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Section: Discussionmentioning

confidence: 94%

Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1−/− Mice by Regulating Macrophage M2 Polarization

et al. 2023

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“…The tissue CatL protein hydrolysis pathway is intricately involved in the regulation of podocyte foot process skeleton proteins. CatL belongs to a subclass of cysteine lysosomal proteases found in tubular epithelial cells and plays multifaceted roles in various physiological and pathological processes, including atherosclerosis, cancer metastasis, rheumatoid arthritis, and nephropathy [ 42 ]. CatL contributes to the degradation of synaptopodin in podocytes and is normally expressed at low levels.…”

Section: Discussionmentioning

confidence: 99%

Klotho Stabilizes the Podocyte Actin Cytoskeleton in Idiopathic Membranous Nephropathy through Regulating the TRPC6/CatL Pathway

Wang,

Liu,

Cheng

et al. 2024

Am J Nephrol

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Introduction: The aim of this study was to explore the renoprotective effects of Klotho on podocyte injury mediated by complement activation and autoantibodies in idiopathic membranous nephropathy (IMN). Methods: Rat passive Heymann nephritis (PHN) was induced as an IMN model. Urine protein levels, serum biochemistry, kidney histology, and podocyte marker levels were assessed. In vitro, sublytic podocyte injury was induced by C5b-9. The expression of Klotho, transient receptor potential channel 6 (TRPC6), and cathepsin L (CatL); its substrate synaptopodin; and the intracellular Ca2+ concentration were detected via immunofluorescence. RhoA/ROCK pathway activity was measured by an activity quantitative detection kit, and the protein expression of phosphorylated-LIMK1 (p-LIMK1) and p-cofilin in podocytes was detected via Western blotting. Klotho knockdown and overexpression were performed to evaluate its role in regulating the TRPC6/CatL pathway. Results: PHN rats exhibited proteinuria, podocyte foot process effacement, decreased Klotho and Synaptopodin levels, and increased TRPC6 and CatL expression. The RhoA/ROCK pathway was activated by the increased phosphorylation of LIMK1 and cofilin. Similar changes were observed in C5b-9-injured podocytes. Klotho knockdown exacerbated podocyte injury, while Klotho overexpression partially ameliorated podocyte injury. Conclusion: Klotho may protect against podocyte injury in IMN patients by inhibiting the TRPC6/CatL pathway. Klotho is a potential target for reducing proteinuria in IMN patients.

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“…CD2AP is ubiquitously expressed with higher levels in immune cells, epithelial cells as well as neurons. Previous studies have shown that CD2AP is necessary for signaling at the slit diaphragm of kidney [19][20][21]. Haploinsufficiency or homozygous mutation of the human CD2AP leads to renal disease [22].…”

Section: Biochemical Properties Of Cd2apmentioning

confidence: 99%

The role of CD2AP in the Pathogenesis of Alzheimer's Disease

Tao

Chen

2019

Aging and disease

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Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by irreversible decline in cognition with unclear pathogenesis. Recently, accumulating evidence has revealed that CD2 associated protein (CD2AP), a scaffolding molecule regulates signal transduction and cytoskeletal molecules, is implicated in AD pathogenesis. Several single nucleotide polymorphisms (SNPs) in CD2AP gene are associated with higher risk for AD and mRNA levels of CD2AP are decreased in peripheral lymphocytes of sporadic AD patients. Furthermore, CD2AP loss of function is linked to enhanced Aβ production, Tau-induced neurotoxici ty, abnormal neurite structure modulation and reduced blood-brain barrier integrity. This review is to summarize the recent discoveries about the genetics and known functions of CD2AP. The recent evidence concerning the roles of CD2AP in the AD pathogenesis is summarized and CD2AP can be a promising therapeutic target for AD.

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CD2AP, Dendrin, and Cathepsin L in the Kidney

Cited by 8 publications

References 7 publications

Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1−/− Mice by Regulating Macrophage M2 Polarization

Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1−/− Mice by Regulating Macrophage M2 Polarization

Klotho Stabilizes the Podocyte Actin Cytoskeleton in Idiopathic Membranous Nephropathy through Regulating the TRPC6/CatL Pathway

The role of CD2AP in the Pathogenesis of Alzheimer's Disease

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