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Start Over Author "Eugen Widmeier" Journal nature communications
2 results on '"Eugen Widmeier"'

1. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment

Author

Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A. Lawson, Weizhen Tan, Tobias Hermle, Jillian K. Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A. Braun, Heon Yung Gee, David Schapiro, Amar J. Majmundar, Carolin E. Sadowski, Werner L. Pabst, Ankana Daga, Amelie T. van der Ven, Johanna M. Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K. Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A. Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A. Soliman, Shrikant M. Mane, Lewis Kaufman, Douglas R. Lowy, Mohamad A. Jairajpuri, Richard P. Lifton, York Pei, Martin Zenker, Shigeo Kure, and Friedhelm Hildebrandt

Subjects
Science
Abstract

Nephrotic syndrome is the second most common chronic kidney disease but there are no targeted treatment strategies available. Here the authors identify mutations of six genes codifying for proteins involved in cytoskeleton remodelling and modulation of small GTPases in 17 families with nephrotic syndrome.

Published
2018
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2. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment

Author

Yasuko Kobayashi, Heon Yung Gee, Juergen Strehlau, York Pei, Shigeo Kure, Therese Jungraithmayr, Kirk N. Campbell, Shirlee Shril, Assel Rakhmetova, Weizhen Tan, Henry Fehrenbach, Mohamad Aman Jairajpuri, Amelie T. van der Ven, Sharon Rose Wassmer, Aravind Selvin Kumar, Friedhelm Hildebrandt, Naonori Kumagai, Neveen A. Soliman, Tilman Jobst-Schwan, Shrikant M. Mane, Jennifer A. Lawson, Atsuo Kikuchi, Ankana Daga, Boon Chuan Low, Hildegard Zappel, Denny Schanze, Martin Zenker, Svjetlana Lovric, Sherif El Desoky, Natasa Stajic, Kandai Nozu, Lewis Kaufman, Jameela A. Kari, Hiroki Kudo, Carolin E. Sadowski, Hiroyasu Tsukaguchi, Jenny Wong, Takumi Takizawa, Jillian K. Warejko, Kazumoto Iijima, Kay Metcalfe, David Schapiro, Daniela A. Braun, Johanna Magdalena Schmidt, Tobias Hermle, Brajendra K. Tripathi, Hiroshi Kaito, Eugen Widmeier, Radovan Bogdanovic, Merlin Airik, Douglas R. Lowy, Keiko Nakayama, Werner L. Pabst, Ryo Funayama, Arvind Bagga, Amar J. Majmundar, Ryojiro Tanaka, Richard P. Lifton, Tetsuya Niihori, Jia Rao, Kiyoshi Hamahira, Sawsan M Jalalah, Yoko Aoki, Anjali Gupta, and Shazia Ashraf

Subjects
Male, 0301 basic medicine, Nephrotic Syndrome, RHOA, Chemistry(all), DNA Mutational Analysis, Drug Resistance, 030232 urology & nephrology, General Physics and Astronomy, medicine.disease_cause, GTP Phosphohydrolases, Mice, 0302 clinical medicine, Small GTPase, Protein Interaction Maps, RNA, Small Interfering, lcsh:Science, Child, Mice, Knockout, Mutation, Gene knockdown, Multidisciplinary, biology, Podocytes, High-Throughput Nucleotide Sequencing, Middle Aged, Phenotype, Pedigree, 3. Good health, Cell biology, Treatment Outcome, Child, Preschool, Gene Knockdown Techniques, Knockout mouse, Female, Guanine nucleotide exchange factor, Adult, Science, Nephrosis, Physics and Astronomy(all), Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Exome Sequencing, medicine, Animals, Humans, Glucocorticoids, Biochemistry, Genetics and Molecular Biology(all), Infant, General Chemistry, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, HEK293 Cells, 030104 developmental biology, biology.protein, lcsh:Q, rhoA GTP-Binding Protein
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., Nephrotic syndrome is the second most common chronic kidney disease but there are no targeted treatment strategies available. Here the authors identify mutations of six genes codifying for proteins involved in cytoskeleton remodelling and modulation of small GTPases in 17 families with nephrotic syndrome.

Published
2018

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