PMID- 34229478
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20210923
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 321
IP  - 2
DP  - 2021 Aug 1
TI  - HIF-1alpha is transcriptionally regulated by NF-kappaB in acute kidney injury.
PG  - F225-F235
LID - 10.1152/ajprenal.00119.2021 [doi]
AB  - Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute 
      kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) 
      is a master regulator of adaptive responses to hypoxia. Aside from 
      posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains 
      largely unclear. In this study, the mechanism of HIF-alpha regulation in AKI was 
      investigated. We found that tubular HIF-1alpha expression significantly increased at 
      the transcriptional level in ischemia-reperfusion-, unilateral ureteral 
      obstruction-, and sepsis-induced AKI models, which was closely associated with 
      macrophage-dependent inflammation. Meanwhile, NF-kappaB, which plays a central role 
      in the inflammation response, was involved in the increasing expression of HIF-1alpha 
      in AKI, as evidenced by pharmacological modulation (NF-kappaB inhibitor BAY11-7082). 
      Mechanistically, NF-kappaB directly bound to the HIF-1alpha promoter and enhanced its 
      transcription, which occurred not only under hypoxic conditions but also under 
      normoxic conditions. Moreover, the induced HIF-1alpha by inflammation protected 
      against tubular injury in AKI. Thus, our findings not only provide novel insights 
      into HIF-1 regulation in AKI but also offer to understand the pathophysiology of 
      kidney diseases.NEW & NOTEWORTHY Here, the mechanism of hypoxia-inducible 
      factor-alpha (HIF-alpha) regulation in acute kidney injury (AKI) was investigated. We 
      found that tubular HIF-1alpha expression significantly increased at the 
      transcriptional level, which was closely associated with macrophage-dependent 
      inflammation. Meanwhile, NF-kappaB was involved in the increasing expression of 
      HIF-1alpha in AKI. Mechanistically, NF-kappaB directly bound to the HIF-1alpha promoter and 
      enhanced its transcription. Our findings not only provide novel insights into 
      HIF-1 regulation in AKI but also offer to understand the pathophysiology of 
      kidney diseases.
FAU - Li, Zuo-Lin
AU  - Li ZL
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Ji, Jia-Ling
AU  - Ji JL
AD  - Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing 
      Medical University, Nanjing, Jiangsu, People's Republic of China.
FAU - Wen, Yi
AU  - Wen Y
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Cao, Jing-Yuan
AU  - Cao JY
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Kharbuja, Naresh
AU  - Kharbuja N
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Ni, Wei-Jie
AU  - Ni WJ
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Yin, Di
AU  - Yin D
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Feng, Song-Tao
AU  - Feng ST
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Liu, Hong
AU  - Liu H
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Lv, Lin-Li
AU  - Lv LL
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Liu, Bi-Cheng
AU  - Liu BC
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Wang, Bin
AU  - Wang B
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University School of 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
LA  - eng
SI  - figshare/10.6084/m9.figshare.14877291.v1
SI  - figshare/10.6084/m9.figshare.14877318.v1
SI  - figshare/10.6084/m9.figshare.14877375.v1
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210706
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Sulfones)
SB  - IM
CIN - Am J Physiol Renal Physiol. 2021 Sep 1;321(3):F255-F256. PMID: 34282955
MH  - Acute Kidney Injury/genetics/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Inflammation/genetics/metabolism
MH  - Kidney/drug effects/*metabolism
MH  - Mice
MH  - NF-kappa B/antagonists & inhibitors/genetics/*metabolism
MH  - Nitriles/pharmacology
MH  - Sulfones/pharmacology
OTO - NOTNLM
OT  - NF-kappaB
OT  - acute kidney injury
OT  - hypoxia-inducible factor-1alpha
OT  - transcriptional regulation
EDAT- 2021/07/08 06:00
MHDA- 2021/09/24 06:00
CRDT- 2021/07/07 05:32
PHST- 2021/07/08 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2021/07/07 05:32 [entrez]
AID - 10.1152/ajprenal.00119.2021 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2021 Aug 1;321(2):F225-F235. doi: 
      10.1152/ajprenal.00119.2021. Epub 2021 Jul 6.