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An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy.
Kato, Mitsuo; Wang, Mei; Chen, Zhuo; Bhatt, Kirti; Oh, Hyung Jung; Lanting, Linda; Deshpande, Supriya; Jia, Ye; Lai, Jennifer Y C; O'Connor, Christopher L; Wu, YiFan; Hodgin, Jeffrey B; Nelson, Robert G; Bitzer, Markus; Natarajan, Rama.
Afiliação
  • Kato M; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Wang M; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Chen Z; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Bhatt K; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Oh HJ; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Lanting L; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Deshpande S; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Jia Y; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
  • Lai JY; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • O'Connor CL; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Wu Y; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Hodgin JB; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Nelson RG; Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014, USA.
  • Bitzer M; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Natarajan R; Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
Nat Commun ; 7: 12864, 2016 Sep 30.
Article em En | MEDLINE | ID: mdl-27686049
ABSTRACT
It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including renal extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that a megacluster of nearly 40 microRNAs and their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli of mouse models of DN, and mesangial cells treated with transforming growth factor-ß1 (TGF- ß1) or high glucose. Lnc-MGC is regulated by an endoplasmic reticulum (ER) stress-related transcription factor, CHOP. Cluster microRNAs and lnc-MGC are decreased in diabetic Chop-/- mice that showed protection from DN. Target genes of megacluster microRNAs have functions related to protein synthesis and ER stress. A chemically modified oligonucleotide targeting lnc-MGC inhibits cluster microRNAs, glomerular ECM and hypertrophy in diabetic mice. Relevance to human DN is also demonstrated. These results demonstrate the translational implications of targeting lnc-MGC for controlling DN progression.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2016 Tipo de documento: Article