https://scholars.lib.ntu.edu.tw/handle/123456789/452402
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | I-JUNG TSAI | en_US |
dc.contributor.author | Chou C.-H. | en_US |
dc.contributor.author | YAO-HSU YANG | en_US |
dc.contributor.author | WEI-CHOU LIN | en_US |
dc.contributor.author | YEN-HUNG LIN | en_US |
dc.contributor.author | LU-PING CHOW | en_US |
dc.contributor.author | Lee H.-H. | en_US |
dc.contributor.author | Kao P.-G. | en_US |
dc.contributor.author | Liau W.-T. | en_US |
dc.contributor.author | TZUU-SHUH JOU | en_US |
dc.contributor.author | Tsau Y.-K. | en_US |
dc.creator | Tsai I.-J.;Chou C.-H.;Yang Y.-H.;Lin W.-C.;Lin Y.-H.;Lu-Ping Chow;Lee H.-H.;Kao P.-G.;Liau W.-T.;Jou T.-S.;Tsau Y.-K. | - |
dc.date.accessioned | 2020-01-22T04:47:49Z | - |
dc.date.available | 2020-01-22T04:47:49Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1420682X | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937736898&doi=10.1007%2fs00018-015-1888-0&partnerID=40&md5=479974c4ef4a75072b44d125732b58b4 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/452402 | - |
dc.description.abstract | Childhood nephrotic syndrome is mainly caused by minimal change disease which is named because only subtle ultrastructural alteration could be observed at electron microscopic level in the pathological kidney. Glomerular podocytes are presumed to be the target cells whose protein sieving capability is compromised by a yet unidentified permeability perturbing factor. In a cohort of children with non-hereditary idiopathic nephrotic syndrome, we found the complement fragment C5a was elevated in their sera during active disease. Administration of recombinant C5a induced profound proteinuria and minimal change nephrotic syndrome in mice. Purified glomerular endothelial cells, instead of podocytes, were demonstrated to be responsible for the proteinuric effect elicited by C5a. Further studies depicted a signaling pathway involving Rho/Rho-associated kinase/myosin activation leading to endothelial cell contraction and cell adhesion complex breakdown. Significantly, application of Rho-associated kinase inhibitor, Y27632, prevented the protein leaking effects observed in both C5a-treated purified endothelial cells and mice. Taken together, our study identifies a previously unknown mechanism underlying nephrotic syndrome and provides a new insight toward identifying Rho-associated kinase inhibition as an alternative therapeutic option for nephrotic syndrome. ? 2015 Springer Basel. | - |
dc.publisher | Birkhauser Verlag AG | - |
dc.relation.ispartof | Cellular and Molecular Life Sciences | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide; complement component C5a; myosin; Rho kinase; 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide; amide; complement component C5a; cytokine; primer DNA; pyridine derivative; recombinant protein; Rho kinase; animal cell; animal experiment; animal model; animal tissue; Article; blood analysis; cell adhesion; cohort analysis; controlled study; drug mechanism; endothelium cell; enzyme activation; enzyme inhibition; kidney disease; male; mouse; nephrotic syndrome; nonhuman; permeability; podocyte; protein losing nephropathy; protein synthesis; proteinuria; purification; relapse; remission; signal transduction; analysis of variance; animal; antagonists and inhibitors; child; complication; cytology; drug effects; enzyme immunoassay; genetics; glomerulus; human; Institute for Cancer Research mouse; metabolism; nephrotic syndrome; proteinuria; reverse transcription polymerase chain reaction; transmission electron microscopy; ultrastructure; Western blotting; Murinae; Mus; Amides; Analysis of Variance; Animals; Blotting, Western; Child; Complement C5a; Cytokines; DNA Primers; Endothelial Cells; Humans; Immunoenzyme Techniques; Kidney Glomerulus; Mice; Mice, Inbred ICR; Microscopy, Electron, Transmission; Nephrotic Syndrome; Proteinuria; Pyridines; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases | - |
dc.title | Inhibition of Rho-associated kinase relieves C5a-induced proteinuria in murine nephrotic syndrome | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1007/s00018-015-1888-0 | - |
dc.identifier.scopus | 2-s2.0-84937736898 | - |
dc.relation.pages | 3157-3171 | - |
dc.relation.journalvolume | 72 | - |
dc.relation.journalissue | 16 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Pediatrics | - |
crisitem.author.dept | Pediatrics-NTUH | - |
crisitem.author.dept | Pediatrics | - |
crisitem.author.dept | Pediatrics-NTUH | - |
crisitem.author.dept | Pathology | - |
crisitem.author.dept | Pathology-NTUH | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.dept | Biochemistry and Molecular Biology | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.orcid | 0000-0003-3967-9412 | - |
crisitem.author.orcid | 0000-0002-6266-9864 | - |
crisitem.author.orcid | 0000-0003-2857-3479 | - |
crisitem.author.orcid | 0000-0001-8153-1441 | - |
crisitem.author.orcid | 0000-0002-4420-211X | - |
crisitem.author.orcid | 0000-0003-4341-5137 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 生物化學暨分子生物學科研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。