Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quin...

Full description

Bibliographic Details
Main Authors:	Jin, Jianliang, Lv, Xianhui, Chen, Lulu, Zhang, Wei, Li, Jinbo, Wang, Qian, Wang, Rong, Lu, Xiang, Miao, Dengshun
Format:	Online
Language:	English
Published:	BlackWell Publishing Ltd 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331754/

id	pubmed-4331754
recordtype	oai_dc
spelling	pubmed-43317542015-02-19 Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance Jin, Jianliang Lv, Xianhui Chen, Lulu Zhang, Wei Li, Jinbo Wang, Qian Wang, Rong Lu, Xiang Miao, Dengshun Original Articles To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. BlackWell Publishing Ltd 2014-10 2014-06-11 /pmc/articles/PMC4331754/ /pubmed/24915841 http://dx.doi.org/10.1111/acel.12236 Text en © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jin, Jianliang Lv, Xianhui Chen, Lulu Zhang, Wei Li, Jinbo Wang, Qian Wang, Rong Lu, Xiang Miao, Dengshun
spellingShingle	Jin, Jianliang Lv, Xianhui Chen, Lulu Zhang, Wei Li, Jinbo Wang, Qian Wang, Rong Lu, Xiang Miao, Dengshun Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
author_facet	Jin, Jianliang Lv, Xianhui Chen, Lulu Zhang, Wei Li, Jinbo Wang, Qian Wang, Rong Lu, Xiang Miao, Dengshun
author_sort	Jin, Jianliang
title	Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
title_short	Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
title_full	Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
title_fullStr	Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
title_full_unstemmed	Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
title_sort	bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance
description	To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury.
publisher	BlackWell Publishing Ltd
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331754/
_version_	1613189493348630528

Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

Similar Items