Cited 85 times in
Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment
DC Field | Value | Language |
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dc.contributor.author | 지헌영 | - |
dc.date.accessioned | 2018-08-28T17:25:16Z | - |
dc.date.available | 2018-08-28T17:25:16Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/162582 | - |
dc.description.abstract | No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Pharmacology | - |
dc.contributor.googleauthor | Shazia Ashraf | - |
dc.contributor.googleauthor | Hiroki Kudo | - |
dc.contributor.googleauthor | Jia Rao | - |
dc.contributor.googleauthor | Atsuo Kikuchi | - |
dc.contributor.googleauthor | Eugen Widmeier | - |
dc.contributor.googleauthor | Jennifer A Lawson | - |
dc.contributor.googleauthor | Weizhen Tan | - |
dc.contributor.googleauthor | Tobias Hermle | - |
dc.contributor.googleauthor | Jillian K Warejko | - |
dc.contributor.googleauthor | Shirlee Shril | - |
dc.contributor.googleauthor | Merlin Airik | - |
dc.contributor.googleauthor | Tilman Jobst-Schwan | - |
dc.contributor.googleauthor | Svjetlana Lovric | - |
dc.contributor.googleauthor | Daniela A Braun | - |
dc.contributor.googleauthor | Heon Yung Gee | - |
dc.contributor.googleauthor | David Schapiro | - |
dc.contributor.googleauthor | Amar J Majmundar | - |
dc.contributor.googleauthor | Carolin E Sadowski | - |
dc.contributor.googleauthor | Werner L Pabst | - |
dc.contributor.googleauthor | Ankana Daga | - |
dc.contributor.googleauthor | Amelie T van der Ven | - |
dc.contributor.googleauthor | Johanna M Schmidt | - |
dc.contributor.googleauthor | Boon Chuan Low | - |
dc.contributor.googleauthor | Anjali Bansal Gupta | - |
dc.contributor.googleauthor | Brajendra K Tripathi | - |
dc.contributor.googleauthor | Jenny Wong | - |
dc.contributor.googleauthor | Kirk Campbell | - |
dc.contributor.googleauthor | Kay Metcalfe | - |
dc.contributor.googleauthor | Denny Schanze | - |
dc.contributor.googleauthor | Tetsuya Niihori | - |
dc.contributor.googleauthor | Hiroshi Kaito | - |
dc.contributor.googleauthor | Kandai Nozu | - |
dc.contributor.googleauthor | Hiroyasu Tsukaguchi | - |
dc.contributor.googleauthor | Ryojiro Tanaka | - |
dc.contributor.googleauthor | Kiyoshi Hamahira | - |
dc.contributor.googleauthor | Yasuko Kobayashi | - |
dc.contributor.googleauthor | Takumi Takizawa | - |
dc.contributor.googleauthor | Ryo Funayama | - |
dc.contributor.googleauthor | Keiko Nakayama | - |
dc.contributor.googleauthor | Yoko Aoki | - |
dc.contributor.googleauthor | Naonori Kumagai | - |
dc.contributor.googleauthor | Kazumoto Iijima | - |
dc.contributor.googleauthor | Henry Fehrenbach | - |
dc.contributor.googleauthor | Jameela A Kari | - |
dc.contributor.googleauthor | Sherif El Desoky | - |
dc.contributor.googleauthor | Sawsan Jalalah | - |
dc.contributor.googleauthor | Radovan Bogdanovic | - |
dc.contributor.googleauthor | Natasa Stajic | - |
dc.contributor.googleauthor | Hildegard Zappel | - |
dc.contributor.googleauthor | Assel Rakhmetova | - |
dc.contributor.googleauthor | Sharon-Rose Wassmer | - |
dc.contributor.googleauthor | Therese Jungraithmayr | - |
dc.contributor.googleauthor | Juergen Strehlau | - |
dc.contributor.googleauthor | Aravind Selvin Kumar | - |
dc.contributor.googleauthor | Arvind Bagga | - |
dc.contributor.googleauthor | Neveen A Soliman | - |
dc.contributor.googleauthor | Shrikant M Mane | - |
dc.contributor.googleauthor | Lewis Kaufman | - |
dc.contributor.googleauthor | Douglas R Lowy | - |
dc.contributor.googleauthor | Mohamad A Jairajpuri | - |
dc.contributor.googleauthor | Richard P Lifton | - |
dc.contributor.googleauthor | York Pei | - |
dc.contributor.googleauthor | Martin Zenker | - |
dc.contributor.googleauthor | Shigeo Kure | - |
dc.contributor.googleauthor | Friedhelm Hildebrandt | - |
dc.identifier.doi | 10.1038/s41467-018-04193-w | - |
dc.contributor.localId | A03971 | - |
dc.relation.journalcode | J02293 | - |
dc.identifier.eissn | 2041-1723 | - |
dc.identifier.pmid | 29773874 | - |
dc.contributor.alternativeName | Gee, Heon Yung | - |
dc.contributor.affiliatedAuthor | Gee, Heon Yung | - |
dc.citation.volume | 9 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1960 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, Vol.9(1) : 1960, 2018 | - |
dc.identifier.rimsid | 60162 | - |
dc.type.rims | ART | - |
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