Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models. 2016

Xiujin Shen, and Hong Jiang, and Meike Ying, and Zhoutao Xie, and Xiayu Li, and Haibing Wang, and Jie Zhao, and Chuan Lin, and Yucheng Wang, and Shi Feng, and Jia Shen, and Chunhua Weng, and Weiqiang Lin, and Huiping Wang, and Qin Zhou, and Yan Bi, and Meng Li, and Lingyan Wang, and Tongyu Zhu, and Xiaoru Huang, and Hui-Yao Lan, and Jing Zhou, and Jianghua Chen
Kidney Disease Center, First Affiliated Hospital, Zhejiang University, School of Medicine; Key Laboratory of Nephropathy, Zhejiang Province, Hangzhou, Zhejiang, China.

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.

UI MeSH Term Description Entries
D008297 Male Males
D009402 Nephrosis, Lipoid A kidney disease with no or minimal histological glomerular changes on light microscopy and with no immune deposits. It is characterized by lipid accumulation in the epithelial cells of KIDNEY TUBULES and in the URINE. Patients usually show NEPHROTIC SYNDROME indicating the presence of PROTEINURIA with accompanying EDEMA. Glomerulonephritis, Minimal Change,Glomerulopathy, Minimal Change,Nephropathy, Minimal Change,Nephrotic Syndrome, Minimal Change,Idiopathic Minimal Change Nephrotic Syndrome,Minimal Change Disease,Minimal Change Glomerulopathy,Minimal Change Nephrotic Syndrome,Change Diseases, Minimal,Disease, Minimal Change,Diseases, Minimal Change,Glomerulonephritides, Minimal Change,Glomerulopathies, Minimal Change,Lipoid Nephroses,Lipoid Nephrosis,Minimal Change Diseases,Minimal Change Glomerulonephritides,Minimal Change Glomerulonephritis,Minimal Change Nephropathies,Minimal Change Nephropathy,Nephropathies, Minimal Change,Nephroses, Lipoid
D011507 Proteinuria The presence of proteins in the urine, an indicator of KIDNEY DISEASES. Proteinurias
D011692 Puromycin Aminonucleoside PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis. 3'-Amino-3'-deoxy-N,N-dimethyladenosine,Aminonucleoside,3' Amino 3' deoxy N,N dimethyladenosine,Aminonucleoside, Puromycin
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016559 Tacrolimus A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Anhydrous Tacrolimus,FK-506,FK506,FR-900506,Prograf,Prograft,Tacrolimus Anhydrous,Anhydrous, Tacrolimus,FK 506,FR 900506,FR900506,Tacrolimus, Anhydrous
D016572 Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). Cyclosporin A,Ciclosporin,CsA-Neoral,CyA-NOF,Cyclosporin,Cyclosporine A,Neoral,OL 27-400,Sandimmun,Sandimmun Neoral,Sandimmune,CsA Neoral,CsANeoral,CyA NOF,OL 27 400,OL 27400
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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