Expression and significance of mitochondrial transcription factor A in hepatocytes of infants with cholestatic jaundice

Wei LIU; Yu NING; Si CHEN; Wanyi ZHOU; Yan LIU; Binxia BAO; Mingman ZHANG

doi:10.16016/j.1000-5404.201811084

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Expression and significance of mitochondrial transcription factor A in hepatocytes of infants with cholestatic jaundice

Basic Medicine | 更新时间：2026-01-09

- Expression and significance of mitochondrial transcription factor A in hepatocytes of infants with cholestatic jaundice
- Journal of Third Military Medical University Vol. 41, Issue 9, Pages: 859-865(2019)
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院肝胆外科，儿童发育疾病研究教育部重点实验室，儿科学重庆市重点实验室，儿童发育重大疾病国家国际科技合作基地
- 作者简介：
- 基金信息：
  
  the Key Project of National Clinical Key-discipline Construction of China(国卫办医函544);the Project of Science and Technology Plan of Chongqing(CSTC2014yykfA110014)
- DOI：10.16016/j.1000-5404.201811084
  CLC： R322.47;R363.21;R725.757
- Received：12 November 2018，
  
  Revised：2019-02-01，
  
  Published：15 May 2019
- 稿件说明：
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Wei LIU, Yu NING, Si CHEN, et al. Expression and significance of mitochondrial transcription factor A in hepatocytes of infants with cholestatic jaundice[J]. Journal of Third Military Medical University, 2019, 41(9): 859-865.
DOI：

Wei LIU, Yu NING, Si CHEN, et al. Expression and significance of mitochondrial transcription factor A in hepatocytes of infants with cholestatic jaundice[J]. Journal of Third Military Medical University, 2019, 41(9): 859-865. DOI： 10.16016/j.1000-5404.201811084.

摘要

目的

探讨线粒体转录因子A(mitochondrial transcription factor A

mtTFA)在婴儿胆汁淤积性黄疸肝细胞中的表达情况及可能的调控机制。

方法

收集患儿肝脏标本并统计其临床资料；构建由甘氨鹅脱氧胆酸(glycochenodeoxycholic acid

GCDCA)诱导的人正常肝细胞(L02)胆汁淤积模型；HE染色检测患儿肝脏的形态学改变；Real-time PCR、qRT-PCR测定患儿肝细胞线粒体DNA(mitochondral DNA

mtDNA)拷贝数和转录水平以及mtTFA和沉默信息调节因子2相关酶类1(silent mating type information regulator 2 homolog 1

SIRT1)通路相关mRNA水平的变化；Western blot测定mtTFA和SIRT1通路相关蛋白水平的变化。

结果

统计病例资料结果显示，黄疸组肝功较对照组明显下降(

0.000 1)；HE染色结果显示，黄疸组肝细胞形态结构紊乱，胆色素沉积，内见胆汁淤积；Real-time PCR、qRT-PCR结果显示，黄疸组肝细胞mtDNA拷贝数与转录水平显著下降(

0.01)，mtTFA、SIRT1和氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptor gamma coactivator-1α

PGC-1α)mRNA水平明显降低(

0.05)；Western blot检测结果显示，黄疸组肝细胞、GCDCA诱导的L02细胞中mtTFA与SIRT1蛋白水平均显著下降(

0.01)，而PGC-1α差异无统计学意义(

0.05)，SRT1720激动SIRT1后mtTFA蛋白的表达较前明显升高(

0.05)。

结论

mtTFA在婴儿胆汁淤积性黄疸肝细胞中的表达显著下降，SIRT1信号通路可能对mtTFA的表达具有调控作用。

Abstract

Objective

To investigate the expression of mitochondrial transcription factor A (mtTFA) in hepatocytes of infants with cholestatic jaundice and explore the possible regulatory mechanism.

Methods

The liver samples and clinical data of the infants with cholestatic jaundice were collected; The cholestatic model of glycochenodeoxycholic acid (GCDCA)-induced human normal hepatocyte (L02) was constructed. HE staining was used to detect morphological changes of the liver tissues. Real-time PCR and qRT-PCR were adopted to detect the mitochondral DNA (mtDNA) copy number and transcription level

and mRNA levels of mtTFA and silent mating type information regulator 2 homolog 1 (SIRT1) pathway-related genes. Western blotting was used to measure the protein levels of mtTFA and SIRT1 pathway-related proteins.

Results

Clinical statistics presented that liver function of the jaundice group was significantly lowe

r than that of control group (

0.000 1). HE staining showed that the jaundice group had hepatocyte morphology disorder

bile pigmentation and intracellular cholestasis. The results of real-time PCR and qRT-PCR demonstrated that the mtDNA copy number and the transcriptional level of mtDNA in the hepatocytes were significantly lower in jaundice group (

0.01)

and the mRNA levels of mtTFA

SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) were significantly decreased in jaundice group (

0.05); Western blot analysis showed that the protein levels of mtTFA and SIRT1 were significantly decreased in the liver tissues of the jaundice group and GCDCA-induced L02 cells (

0.001)

but that of PGC-1α had no statistical difference (

0.05). Treatment with SIRT1 agonist SRT1720 resulted in increased expression level of mtTFA protein (

0.05).

Conclusion

The expression level of mtTFA is obviously decreased in hepatocytes of infants with cholestatic jaundice

and SIRT1 signaling pathway may play a regulatory role in its expression.

关键词

Keywords

references

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