TGF-β1 signaling mediated hepatic stellate cells promote hepatic progenitor cells differentiation into cholangiocytes

您当前的位置：

首页 >

文章列表页 >

TGF-β1 signaling mediated hepatic stellate cells promote hepatic progenitor cells differentiation into cholangiocytes

Basic Medicine | 更新时间：2026-01-09

- TGF-β1 signaling mediated hepatic stellate cells promote hepatic progenitor cells differentiation into cholangiocytes
- Journal of Third Military Medical University Vol. 40, Issue 9, Pages: 746-752(2018)
- 作者机构：
  
  400016 重庆, 重庆医科大学附属第一医院肝胆外科, 实验研究中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81470898)
- DOI：10.16016/j.1000-5404.201711122
  CLC： R322.47;R329-33;R329.26
- Received：15 November 2017，
  
  Revised：2018-02-28，
  
  Published：15 May 2018
- 稿件说明：
移动端阅览
AI MAITI·Ya Sen, Xin JIN, Zixin CHEN, et al. TGF-β1 signaling mediated hepatic stellate cells promote hepatic progenitor cells differentiation into cholangiocytes[J]. Journal of Third Military Medical University, 2018, 40(9): 746-752.
DOI：

AI MAITI·Ya Sen, Xin JIN, Zixin CHEN, et al. TGF-β1 signaling mediated hepatic stellate cells promote hepatic progenitor cells differentiation into cholangiocytes[J]. Journal of Third Military Medical University, 2018, 40(9): 746-752. DOI： 10.16016/j.1000-5404.201711122.

摘要

目的

2

探讨转化生长因子β1 (transforming growth factor β1

TGF-β1)激活的小鼠肝星状细胞(mouse hepatic stellate cells

mHSCs)对小鼠胚胎肝前体细胞(mouse hepatic progenitor cells

mHPCs)分化的影响。

方法

2

mHSCs细胞株加入10 ng/mL TGF-β1刺激48 h

并分为激活组(mHSCs-TGF-β1)和对照组(mHSCs)。qRT-PCR和Western blot法检测mHSCs激活情况。采用荧光激活细胞筛选法(fluorescence-activated cell sorter

FACS)分选DLK1(delta-like1 homologue)表面抗原阳性的原代mHPCs

分选的细胞利用免疫荧光染色法观察甲胎蛋白(alpha-fetoprotein

AFP)、白蛋白(albumin

ALB)及细胞角蛋白19(cytokeratin 19

CK19)抗原表达情况。mHPCs与mHSCs Transwell共培养6 d后

分为mHPCs+mHSCs-TGF-β1组、mHPCs+mHSCs组和mHPCs组。细胞免疫荧光技术法和qRT-PCR法检测分化标志物表达情况。

结果

2

激活组mHSCs中TGF-β1、α-SMA、TGF-β-R1、Jagged1、VEGF、HGF等mRNA和TGF-β1、a-SMA、TGF-β-R1、Jagged1等蛋白的表达量均较对照组明显增加(

P

<

0.01);FACS新分选的mHPCs胞质中表达AFP和少量ALB

但不表达CK19;mHPCs+mHSCs-TGF-β1组mHPCs胞质中大量表达胆管细胞标志物

并且CK19、SOX9、Hes1等mRNA表达量均较其他两组明显增加

而其他两组mHPCs中ALB、AFP等的表达量明显增加(

P

<

0.01)。

结论

2

TGF-β1激活的肝星状细胞诱导胚胎肝前体细胞向胆管细胞分化。

Abstract

Objective

2

To investigate the effects of mouse hepatic stellate cells (mHSCs) activated by transcription factor β1 (TGF-β1) on mouse hepatic progenitor cells (mHPCs) differentiation.

Methods

2

After the mHSCs were treated with 10 ng/mL TGF-β1 for 48 h

the cells were assigned into activation group (mHSCs-TGF-β1)

and those without treatment served as control group (mHSCs).Activation of mHSCs was detected by qRT-PCR and Western blotting.mHPCs were isolated from fetal livers based on the cell surface antigen delta-like protein 1 (Dlk1) by a fluorescence-activated cell sorter (FACS)

and the expression of alpha-fetoprotein (AFP)

albumin (ALB)

and cytokeratin 19 (CK19) was observed by immunocytochemical assay.Then the obtained mHPCs and mHSCs were co-cultured in a Transwell system for 6 d.Immunocytochemical assay and qRT-PCR were used to detect the expression of differentiation markers in mHPCs+mHSCs-TGF-β1 group

mHPCs+mHSCs group and mHPCs group.

Results

2

The mRNA levels of a-SMA

TGF-β1

TGF-β-R1

Jagged1

HGF and VEGF

and protein levels of TGF-β1

a-SMA

TGF-β-R1 and Jagged1 were significantly higher in the activation group (

P

<

0.01);Freshly sorted mHPCs by FACS expressed AFP and low level of ALB but not CK19 in the cytoplasm.In the mHPCs+mHSCs-TGF-β1 group

mHPCs highly expressed duct-specific markers in the cytoplasm

and the mRNA levels of CK19

SOX9 and Hes1 were obviously higher than the other 2 groups of cells. But the ALB and AFP expression was more obvious in the 2 groups (

P

<

0.01).

Conclusion

2

TGF-β1-activated hepatic stellate cells induce hepatic progenitor cells differentiation into cholangiocytes.

关键词

Keywords

references

KAMIYA A, INAGAKI Y.Stem and progenitor cell systems in liver development and regeneration[J].Hepatol Res, 2015, 45(1):29-37.DOI:10.1111/hepr.12349.

SANCHO-BRU P, NAJIMI M, CARUSO M, et al .Stem and progenitor cells for liver repopulation:can we standardise the process from bench to bedside[J ] .Gut, 2009, 58(4):594-603.DOI:10.1136/gut.2008.171116.

PINTILIE D G, SHUPE T D, OH S H, et al .Hepatic stellate cells' involvement in progenitor-mediated liver regeneration[J ] .Lab Invest, 2010, 90(8):1199-1208.DOI:10.1038/labinvest.2010.88.

GORDILLO M, EVANS T, GOUON-EVANS V.Orchestrating liver development[J].Development, 2015, 142(12):2094-2108.DOI:10.1242/dev.114215.

SUZUKI K, TANAKA M, WATANABE N, et al .p75 neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver[J ] .Gastroenterol, 2008, 135(1):270-281.e3.DOI:10.1053/j.gastro.2008.03.075.

TANIMIZU N, SAITO H, MOSTOV K, et al .Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts[J ] .J Cell Sci, 2004, 117(Pt 26):6425-6434.DOI:10.1242/jcs.01572.

WEIS S M, CHERESH D A.Tumor angiogenesis:molecular pathways and therapeutic targets[J].Nature Med, 2011, 17(11):1359-1370.DOI:10.1038/nm.2537.

FURUYAMA K, KAWAGUCHI Y, AKIYAMA H, et al .Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine[J ] .Nat Genet, 2010, 43(1):34-41.DOI:10.1038/ng.722.

HABIBULLAH C M, SYED I H, QAMAR A, et al .Human fetal hepatocyte transplantation in patients with fulminant hepatic failure[J ] .Transplantation, 1994, 58(8):951-952.DOI:10.1097/00007890-199410270-00016.

ISHII T, YASUCHIKA K, MACHIMOTO T, et al .Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage[J ] .Stem Cells, 2007, 25(12):3252-3260.DOI:10.1634/stemcells.2007-0199.

KALINICHENKO V V, BHATTACHARYYA D, ZHOU Y, et al .Foxf1 +/-mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury[J ] .Hepatology, 2003, 37(1):107-117.DOI:10.1053/jhep.2003.50005.

LORENZINI S, BIRD T G, BOULTER L, et al .Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver[J ] .Gut, 2010, 59(5):645-654.DOI:10.1136/gut.2009.182345.

BAI S, KOPAN R, ZOU W, et al .NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells[J ] .J Biol Chem, 2008, 283(10):6509-6518.DOI:10.1074/jbc.M707000200..

HU K F, KONG X Y, ZHONG M C, et al .Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways[J ] .Chin J Integr Med, 2017, 23(2):110-116.DOI:10.1007/s11655-016-2647-2.

肖斌, 陈川宁, 陶忠桦, 等.Notch通路对乙醛激活大鼠肝星状细胞株的增殖及转分化的影响[J].中国老年学杂志, 2014, 34(3):710-713.

XIAO B, CHEN C N, TAO Z H, et al .The role of notch pathway in hepatic stellate cell strain [J ] .Chin J Gerontol, 2014, 34(3):710-713.

ANTONIOU A, RAYNAUD P, CORDI S, et al .Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9[J ] .Gastroenterology, 2009, 136(7):2325-2333.DOI:10.1053/j.gastro.2009.02.051.

KOBAYASHI T, MIZUNO H, IMAYOSHI I, et al .The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells[J ] .Gene Develop, 2009, 23(16):1870-1875.DOI:10.1101/gad.1823109.

KAKINUMA S, NAKAUCHI H, WATANABE M.Hepatic stem/progenitor cells and stem-cell transplantation for the treatment of liver disease[J].J Gastroenterol, 2009, 44(3):167-172.DOI:10.1007/s00535-008-2297-z.

0

Views

0

下载量

0

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

Effect and underlying mechanism of thrombospondin-1 knockout on radiation-induced pulmonary fibrosis in mice

RANKL inhibits activation of hepatic stellate cells during hepatic fibrosis in mice

Effects of hyperglycemia and macrophage co-culture on oxidative stress and autophagy in osteoblasts

TSSC3 suppresses fibrosis of renal tubular epithelium by regulating PI3K/Akt signaling pathway and anoikis resistance in myofibroblasts

Effect of S100A6 on activation of hepatic stellate cells in mice

Related Author

焦露

李杰

张静

陈用来

郝玉徽

周丽佳

钟立

薛倩

Related Institution

Department of Cardiology, Chongqing Institute of Interventional Cardiology, First Affiliated Hospital, Army Medical University (Third Military Medical University)

⁰