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胆管纤维化模型中大鼠肝卵圆细胞的超微结构特征及其细胞间接触：对实验性肝纤维化形成的新见解

Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis.

作者信息

Lotowska Joanna Maria, Sobaniec-Lotowska Maria Elzbieta, Lebensztejn Dariusz Marek, Daniluk Urszula, Sobaniec Piotr, Sendrowski Krzysztof, Daniluk Jaroslaw, Reszec Joanna, Debek Wojciech

机构信息

Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.

Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland.

出版信息

Gastroenterol Res Pract. 2017;2017:2721547. doi: 10.1155/2017/2721547. Epub 2017 Jul 9.

DOI:10.1155/2017/2721547
PMID:28769978
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5523291/
Abstract

PURPOSE

Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL).

METHODS

The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks.

RESULTS

Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis. HPCs formed proliferating bile ductules and were scattered in periportal connective tissue. We distinguished 4 main types of HPCs: 0, I, II (bile duct-like cells; most common), and III (hepatocyte-like cells). We observed, very seldom presented in literature, cellular interactions between HPCs and adjacent NPCs, especially commonly found transitional hepatic stellate cells (T-HSCs) and Kupffer cells/macrophages. We showed the phenomenon of penetration of the basement membrane of proliferating bile ductules by cytoplasmic processes sent by T-HSCs and the formation of direct cell-cell contact with ductular epithelial cells related to HPCs.

CONCLUSIONS

HPC proliferation induced by BDL evidently promotes portal fibrogenesis. Better understanding of the complex cellular interactions between HPCs and adjacent NPCs, especially T-HSCs, may help develop antifibrotic therapies in the future.

摘要

目的

最近，有研究强调肝祖细胞/卵圆细胞（HPCs）在肝纤维化形成过程中发挥着重要作用。我们通过透射电子显微镜（TEM）评估了HPCs的多能细胞群，包括其与胆管结扎（BDL）诱导的胆汁性肝纤维化大鼠中黏附性肝非实质细胞（NPCs）的关系。

方法

本研究使用6周龄的Wistar Crl:WI（Han）大鼠，在BDL术后1、6和8周进行观察。

结果

目前的超微结构分析显示，在实验性重度胆汁性肝纤维化中，HPCs有显著增殖。HPCs形成增生的胆小管，并散在于汇管区结缔组织中。我们区分出4种主要类型的HPCs：0型、I型、II型（胆管样细胞；最常见）和III型（肝细胞样细胞）。我们观察到HPCs与相邻NPCs之间的细胞相互作用，尤其是常见的过渡性肝星状细胞（T-HSCs）和库普弗细胞/巨噬细胞，这在文献中很少提及。我们发现T-HSCs发出的细胞质突起穿透增生胆小管的基底膜，并与HPCs相关的胆小管上皮细胞形成直接的细胞间接触。

结论

BDL诱导的HPCs增殖明显促进门脉纤维化形成。更好地理解HPCs与相邻NPCs之间复杂的细胞相互作用，尤其是与T-HSCs之间的相互作用，可能有助于未来开发抗纤维化治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/92b71199d836/GRP2017-2721547.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/9d7f9804788a/GRP2017-2721547.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/3a3e59403d41/GRP2017-2721547.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/92b71199d836/GRP2017-2721547.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/9d7f9804788a/GRP2017-2721547.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/3a3e59403d41/GRP2017-2721547.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0202/5523291/92b71199d836/GRP2017-2721547.003.jpg

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