PMID- 38284121
OWN - NLM
STAT- MEDLINE
DCOM- 20240306
LR  - 20240306
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 326
IP  - 3
DP  - 2024 Mar 1
TI  - HIF-1 contributes to autophagy activation via BNIP3 to facilitate renal fibrosis 
      in hypoxia in vitro and UUO in vivo.
PG  - C935-C947
LID - 10.1152/ajpcell.00458.2023 [doi]
AB  - The molecular basis of renal interstitial fibrosis, a major pathological feature 
      of progressive kidney diseases, remains poorly understood. Autophagy has been 
      implicated in renal fibrosis, but whether it promotes or inhibits fibrosis 
      remains controversial. Moreover, it is unclear how autophagy is activated and 
      sustained in renal fibrosis. The present study was designed to address these 
      questions using the in vivo mouse model of unilateral ureteral obstruction and 
      the in vitro model of hypoxia in renal tubular cells. Both models showed the 
      activation of hypoxia-inducible factor-1 (HIF-1) and autophagy along with 
      fibrotic changes. Inhibition of autophagy with chloroquine reduced renal fibrosis 
      in unilateral ureteral obstruction model, whereas chloroquine and 
      autophagy-related gene 7 knockdown decreased fibrotic changes in cultured renal 
      proximal tubular cells, supporting a profibrotic role of autophagy. Notably, 
      pharmacological and genetic inhibition of HIF-1 led to the suppression of 
      autophagy and renal fibrosis in these models. Mechanistically, knock down of BCL2 
      and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a downstream target gene 
      of HIF, decreased autophagy and fibrotic changes during hypoxia in BUMPT cells. 
      Together, these results suggest that HIF-1 may activate autophagy via BNIP3 in 
      renal tubular cells to facilitate the development of renal interstitial 
      fibrosis.NEW & NOTEWORTHY Autophagy has been reported to participate in renal 
      fibrosis, but its role and underlying activation mechanism is unclear. In this 
      study, we report the role of HIF-1 in autophagy activation in models of renal 
      fibrosis and further investigate the underlying mechanism.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
FAU - Livingston, Man J
AU  - Livingston MJ
AUID- ORCID: 0000-0001-8638-0902
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
FAU - Dong, Guie
AU  - Dong G
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
FAU - Wei, Qingqing
AU  - Wei Q
AUID- ORCID: 0000-0002-1692-2451
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
FAU - Zhang, Ming
AU  - Zhang M
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
FAU - Mei, Shuqin
AU  - Mei S
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
AD  - Department of Nephrology, Second Affiliated Hospital of Naval Medical University, 
      Shanghai, China.
FAU - Zhu, Jiefu
AU  - Zhu J
AD  - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Zhang, Chun
AU  - Zhang C
AUID- ORCID: 0000-0003-3565-8024
AD  - Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Dong, Zheng
AU  - Dong Z
AUID- ORCID: 0000-0003-3538-8095
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States.
LA  - eng
GR  - DK058831;DK087843/HHS | National Institutes of Health (NIH)/
GR  - BX000319/U.S. Department of Veterans Affairs (VA)/
PT  - Journal Article
DEP - 20240129
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Ureteral Obstruction/complications/genetics/metabolism
MH  - Hypoxia-Inducible Factor 1
MH  - *Kidney Diseases/pathology
MH  - Hypoxia
MH  - Autophagy/genetics
MH  - Fibrosis
MH  - Chloroquine/pharmacology
OTO - NOTNLM
OT  - BNIP3
OT  - autophagy
OT  - hypoxia-inducible factor-1
OT  - renal fibrosis
EDAT- 2024/01/29 06:44
MHDA- 2024/03/06 06:43
CRDT- 2024/01/29 04:53
PHST- 2024/03/06 06:43 [medline]
PHST- 2024/01/29 06:44 [pubmed]
PHST- 2024/01/29 04:53 [entrez]
AID - 10.1152/ajpcell.00458.2023 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2024 Mar 1;326(3):C935-C947. doi: 
      10.1152/ajpcell.00458.2023. Epub 2024 Jan 29.