Pyruvate kinase M2 mediates fibroblast proliferation to promote tubular epithelial cell survival in acute kidney injury.
FASEB J
; 35(7): e21706, 2021 07.
Article
in En
| MEDLINE
| ID: mdl-34160104
ABSTRACT
Acute kidney injury (AKI) is a devastating condition with high morbidity and mortality rates. The pathological features of AKI are tubular injury, infiltration of inflammatory cells, and impaired vascular integrity. Pyruvate kinase is the final rate-limiting enzyme in the glycolysis pathway. We previously showed that pyruvate kinase M2 (PKM2) plays an important role in regulating the glycolytic reprogramming of fibroblasts in renal interstitial fibrosis. The present study aimed to determine the role of PKM2 in fibroblast activation during the pathogenesis of AKI. We found increased numbers of S100A4 positive cells expressing PKM2 in renal tissues from mice with AKI induced via folic acid or ischemia/reperfusion (I/R). The loss of PKM2 in fibroblasts impaired fibroblast proliferation and promoted tubular epithelial cell death including apoptosis, necroptosis, and ferroptosis. Mechanistically, fibroblasts produced less hepatocyte growth factor (HGF) in response to a loss of PKM2. Moreover, in two AKI mouse models, fibroblast-specific deletion of PKM2 blocked HGF signal activation and aggravated AKI after it was induced in mice via ischemia or folic acid. Fibroblast proliferation mediated by PKM2 elicits pro-survival signals that repress tubular cell death and may help to prevent AKI progression. Fibroblast activation mediated by PKM2 in AKI suggests that targeting PKM2 expression could be a novel strategy for treating AKI.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyruvate Kinase
/
Cell Survival
/
Cell Proliferation
/
Epithelial Cells
/
Acute Kidney Injury
/
Fibroblasts
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2021
Type:
Article
Affiliation country:
China