PMID- 33987225
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231123
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 7
DP  - 2021 Apr
TI  - Mitochondrial dysfunction attenuates rapid regeneration in livers with 
      toxin-induced fibrosis.
PG  - 527
LID - 10.21037/atm-20-4639 [doi]
LID - 527
AB  - BACKGROUND: The mechanism of associating liver partition and portal vein ligation 
      for staged hepatectomy (ALPPS)-induced rapid liver regeneration remains poorly 
      documented, especially in patients with fibrosis. Therefore, this study aims to 
      investigate the underlying mechanism of ALPPS-induced accelerated regeneration in 
      toxin-induced fibrosis models. METHODS: The ALPPS-induced regeneration model was 
      established in livers with thioacetamide (TAA)-induced fibrosis to determine the 
      regenerative pathways involved in rapid regeneration. Confirmatory experiments 
      were performed in transforming growth factor beta 1 (TGFbeta1)-treated AML12 cells 
      and mice with carbon tetrachloride (CCl(4))-induced fibrosis. Finally, 
      mitochondrial dysfunction was validated in fibrotic/non-fibrotic patients. 
      RESULTS: In TAA-induced fibrotic mice, ALPPS-induced regeneration was 
      significantly inferior to that of the control group (P=0.027 at day 2 and P<0.001 
      at day 7). Furthermore, mitochondria-associated genes were significantly 
      downregulated in TAA-challenged mice. Accordingly, the reduced production of ATP 
      and elevated levels of malondialdehyde indicated disturbances in intracellular 
      energy metabolism during the ALPPS-induced regenerative process after TAA 
      treatment. Further investigations were performed in TGF-beta1-treated AML12 cells 
      and CCl(4)-treated mice, which indicated that mitochondrial dysfunction 
      attenuated the capacity for rapid regeneration after ALPPS. CONCLUSIONS: In 
      summary, this study revealed that mitochondrial dysfunction led to inferior 
      regeneration in livers with toxin-induced fibrosis and identified new therapeutic 
      targets to improve the feasibility and safety of the ALPPS procedure. Further 
      studies in human patients are required in the future.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Li, Zheyong
AU  - Li Z
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Liang, Yuelong
AU  - Liang Y
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Ying, Hanning
AU  - Ying H
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Chen, Mingyu
AU  - Chen M
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - He, Xiaoyan
AU  - He X
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
AD  - Department of Biological Treatment Research Center, Sir Run Run Shaw Hospital, 
      School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Wang, Yifan
AU  - Wang Y
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Tong, Yifan
AU  - Tong Y
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Cai, Xiujun
AU  - Cai X
AD  - Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw 
      Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8105818
OTO - NOTNLM
OT  - Associating liver partition and portal vein ligation for staged hepatectomy 
      (ALPPS)
OT  - fibrosis
OT  - mitochondrial dysfunction
OT  - regeneration
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-20-4639). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/05/15 06:00
MHDA- 2021/05/15 06:01
PMCR- 2021/04/01
CRDT- 2021/05/14 07:02
PHST- 2021/05/14 07:02 [entrez]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2021/05/15 06:01 [medline]
PHST- 2021/04/01 00:00 [pmc-release]
AID - atm-09-07-527 [pii]
AID - 10.21037/atm-20-4639 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Apr;9(7):527. doi: 10.21037/atm-20-4639.