التفاصيل البيبلوغرافية
| العنوان: |
Activation of AMPK-PGC-1α pathway ameliorates peritoneal dialysis related peritoneal fibrosis in mice by enhancing mitochondrial biogenesis. |
| المؤلفون: |
Wu, Jun1 (AUTHOR), Li, Jushuang1 (AUTHOR), Feng, Baohong1 (AUTHOR), Bi, Zhimin1 (AUTHOR), Zhu, Geli1 (AUTHOR), Zhang, Yanxia1 (AUTHOR), Li, Xiangyou1 (AUTHOR) lixiangyou3@163.com |
| المصدر: |
Renal Failure. Dec2022, Vol. 44 Issue 1, p1546-1558. 13p. |
| مصطلحات موضوعية: |
*PERITONEAL dialysis, *RETROPERITONEAL fibrosis, *MITOCHONDRIA, *PEROXISOME proliferator-activated receptors, *MITOCHONDRIAL DNA, *AMP-activated protein kinases |
| مستخلص: |
The pathogenesis of peritoneal dialysis (PD)-related peritoneal fibrosis (PF) is not clearly understood, and current treatment options are limited. In this study, the effect of PD-related PF on mitochondrial biogenesis was investigated, and the effect of activation of the adenosine monophosphate-activated protein kinase (AMPK)-PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) pathway on PF was evaluated in mice. In a mouse model of PD-related PF, AMPK-PGC-1α signaling (phospho-AMPK, PGC-1α, NRF-1, NRF-2 and TFAM expression) was downregulated, mitochondrial DNA (mtDNA) levels were reduced, and mitochondrial structure was damaged in the peritoneum. In addition, TdT-mediated dUTP nick-end labeling (TUNEL) staining showed typical apoptosis characteristics in peritoneal mesothelial cells (PMCs). Activation of the AMPK-PGC-1α pathway (PGC-1α overexpression or metformin, which is an agonist of AMPK) upregulated phospho-AMPK, PGC-1α, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2), and mitochondrial transcription factor A (TFAM) expression and mtDNA content, improved mitochondrial morphological manifestations, inhibited apoptosis of PMCs and alleviated PF. Our study may suggest that activation of the AMPK-PGC-1α pathway ameliorates PD-related PF by enhancing mitochondrial biogenesis. [ABSTRACT FROM AUTHOR] |
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