作为肝储备标志物的肝线粒体形态和基因表达：胆道闭锁患者原肝存活率的预后意义。

IF 2.4 2区医学 Q1 PEDIATRICS

Journal of pediatric surgery Pub Date : 2025-02-01 DOI:10.1016/j.jpedsurg.2024.07.033

Takashi Fujimoto , Hiroki Goto , Masataka Hida , Koichi Tsuboi , Takamasa Suzuki , Hisae Iida , Ayaka Fukada , Sakika Shimizu , Yu Ebata , Koki Nikai , Junya Ishii , Masahiro Takeda , Asuka Ishiyama , Soichi Shibuya , Yuta Yazaki , Nana Nakazawa-Tanaka , Go Miyano , Tadaharu Okazaki , Toshihiro Yanai , Masahiko Urao , Kazuto Suda

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The P-cohort had transmission electron microscopy (TEM) to image mitochondria, immunoblotting for heat shock protein 60 (HSP60), and quantitative PCR (qPCR) for HSP60 and mitochondrial functional genes. Both cohorts had immunofluorescence for HSP60 quantified as a ratio to albumin-positive hepatocytes (ALB) with HSP60/ALB<1.0 as a cutoff limit using ImageJ.</div></div><div><h3>Results</h3><div>HSP60 was significantly lower in BA/IC than NL on qPCR (BA: <em>p</em> < 0.01, IC: <em>p</em> < 0.05) and lower in BA than IC/NL on immunoblotting (<em>p</em> < 0.05). HSP60/ALB was significantly lower in BA than NL/IC (<em>p</em> < 0.001). 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摘要

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Liver Mitochondrial Morphology and Gene Expression as Markers of Liver Reserve: Prognostic Implications for Native Liver Survival in Biliary Atresia

Purpose

Hepatocyte mitochondrial morphology and gene expression were compared between biliary atresia (BA), infantile cholestasis (IC), and normal liver (NL) as prognostic indicators.

Methods

Specimens of liver at portoenterostomy (PE) for BA, from intrahepatic bile duct paucity patients for IC, and from choledochal cyst or hepatoblastoma patients for NL were collected prospectively (P) beginning in 2021 (P-BA = 11, P-IC = 9, P-NL = 7) and retrospectively (R) from paraffin-embedded tissue going back to 1981 (R-BA = 25, R-IC = 9, R-NL = 4). The P-cohort had transmission electron microscopy (TEM) to image mitochondria, immunoblotting for heat shock protein 60 (HSP60), and quantitative PCR (qPCR) for HSP60 and mitochondrial functional genes. Both cohorts had immunofluorescence for HSP60 quantified as a ratio to albumin-positive hepatocytes (ALB) with HSP60/ALB<1.0 as a cutoff limit using ImageJ.

Results

HSP60 was significantly lower in BA/IC than NL on qPCR (BA: p < 0.01, IC: p < 0.05) and lower in BA than IC/NL on immunoblotting (p < 0.05). HSP60/ALB was significantly lower in BA than NL/IC (p < 0.001). Despite BA subjects being matched for types of BA and ages at PE, HSP60/ALB did not correlate with jaundice clearance (JC; T-Bil<1.2 mg/dL) but was significantly higher in native liver survivors (NLS) after PE compared with liver transplant (LTx) cases (p < 0.05) and significantly lower in LTx cases achieving JC than NLS achieving JC (p < 0.05). TEM showed BA had significantly more mitochondrial inclusion bodies (p < 0.05) and significantly larger cristae (p < 0.01) than IC/NL. qPCR in BA showed significant repression of mitochondrial functional genes for mRNA stabilization and energy facilitation.

Conclusion

HSP60/ALB correlates with NLS after PE for BA.

Level of evidence

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来源期刊

Journal of pediatric surgery 医学-外科

CiteScore

1.10

自引率

12.50%

发文量

569

审稿时长

38 days

期刊介绍： The journal presents original contributions as well as a complete international abstracts section and other special departments to provide the most current source of information and references in pediatric surgery. The journal is based on the need to improve the surgical care of infants and children, not only through advances in physiology, pathology and surgical techniques, but also by attention to the unique emotional and physical needs of the young patient.