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Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.
Liu, Min; Liang, Kaili; Zhen, Junhui; Zhou, Meng; Wang, Xiaojie; Wang, Ziying; Wei, Xinbing; Zhang, Yan; Sun, Yu; Zhou, Zhuanli; Su, Hua; Zhang, Chun; Li, Ningjun; Gao, Chengjiang; Peng, Jun; Yi, Fan.
Afiliación
  • Liu M; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Liang K; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Zhen J; Department of Pathology, Shandong University School of Medicine, Jinan, 250012, China.
  • Zhou M; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Wang X; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Wang Z; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Wei X; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Zhang Y; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Sun Y; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China.
  • Zhou Z; Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Su H; Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Zhang C; Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Li N; Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Gao C; Department of Immunology, Shandong University School of Medicine, Jinan, 250012, China.
  • Peng J; Department of Hematology, Qilu Hospital, Shandong University, Jinan, 250012, China.
  • Yi F; Department of Pharmacology, Shandong University School of Medicine, Jinan, 250012, China. fanyi@sdu.edu.cn.
Nat Commun ; 8(1): 413, 2017 09 04.
Article en En | MEDLINE | ID: mdl-28871079
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy. Sirt6 has pleiotropic protective actions in podocytes, including anti-inflammatory and anti-apoptotic effects, is involved in actin cytoskeleton maintenance and promotes autophagy. Sirt6 also reduces urokinase plasminogen activator receptor expression, which is a key factor for podocyte foot process effacement and proteinuria. Mechanistically, Sirt6 inhibits Notch1 and Notch4 transcription by deacetylating histone H3K9. We propose Sirt6 as a potential therapeutic target for the treatment of proteinuric kidney disease.Podocytes are essential components of the renal glomerular filtration barrier and podocyte dysfunction leads to proteinuric kidney disease. Here Liu et al. show that Sirt6 protects podocytes from apoptosis and inflammation by increasing autophagic flux through inhibition of the Notch pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteinuria / Transducción de Señal / Sirtuinas / Podocitos / Receptores Notch Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteinuria / Transducción de Señal / Sirtuinas / Podocitos / Receptores Notch Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido