PMID- 27686049
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220311
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 7
DP  - 2016 Sep 30
TI  - An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster 
      induces early features of diabetic nephropathy.
PG  - 12864
LID - 10.1038/ncomms12864 [doi]
LID - 12864
AB  - 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-beta1 (TGF- beta1) 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.
FAU - Kato, Mitsuo
AU  - Kato M
AUID- ORCID: 0000-0002-1783-1084
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Wang, Mei
AU  - Wang M
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Chen, Zhuo
AU  - Chen Z
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Bhatt, Kirti
AU  - Bhatt K
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Oh, Hyung Jung
AU  - Oh HJ
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Lanting, Linda
AU  - Lanting L
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Deshpande, Supriya
AU  - Deshpande S
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Jia, Ye
AU  - Jia Y
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
FAU - Lai, Jennifer Y C
AU  - Lai JY
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109, USA.
FAU - O'Connor, Christopher L
AU  - O'Connor CL
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109, USA.
FAU - Wu, YiFan
AU  - Wu Y
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109, USA.
FAU - Hodgin, Jeffrey B
AU  - Hodgin JB
AD  - Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
FAU - Nelson, Robert G
AU  - Nelson RG
AD  - Diabetes Epidemiology and Clinical Research Section, National Institute of 
      Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 
      Phoenix, Arizona 85014, USA.
FAU - Bitzer, Markus
AU  - Bitzer M
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 
      48109, USA.
FAU - Natarajan, Rama
AU  - Natarajan R
AD  - Department of Diabetes Complications and Metabolism, Diabetes Metabolism Research 
      Institute, Beckman Research Institute of City of Hope, Duarte, California 91010, 
      USA.
LA  - eng
GR  - R01 DK058191/DK/NIDDK NIH HHS/United States
GR  - R01 DK100449/DK/NIDDK NIH HHS/United States
GR  - R01 DK081705/DK/NIDDK NIH HHS/United States
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - DP3 DK106917/DK/NIDDK NIH HHS/United States
GR  - R01 DK065073/DK/NIDDK NIH HHS/United States
GR  - R01 HL106089/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20160930
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
CIN - Nat Rev Nephrol. 2016 Dec;12(12):713. PMID: 27748387
PMC - PMC5553130
COIS- The authors declare no competing financial interests.
EDAT- 2016/10/01 06:00
MHDA- 2016/10/01 06:01
PMCR- 2016/09/30
CRDT- 2016/10/01 06:00
PHST- 2016/02/22 00:00 [received]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/10/01 06:00 [entrez]
PHST- 2016/10/01 06:00 [pubmed]
PHST- 2016/10/01 06:01 [medline]
PHST- 2016/09/30 00:00 [pmc-release]
AID - ncomms12864 [pii]
AID - 10.1038/ncomms12864 [doi]
PST - epublish
SO  - Nat Commun. 2016 Sep 30;7:12864. doi: 10.1038/ncomms12864.