Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis

Abstract Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are know...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Byeong-Moo Kim, Ahmed Maher Abdelfattah, Robin Vasan, Bryan C. Fuchs, Michael Y. Choi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e37e7fae676a400cb95ddddefd645c5b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e37e7fae676a400cb95ddddefd645c5b
record_format	dspace
spelling	oai:doaj.org-article:e37e7fae676a400cb95ddddefd645c5b2021-12-02T16:08:16ZHepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis10.1038/s41598-018-25699-92045-2322https://doaj.org/article/e37e7fae676a400cb95ddddefd645c5b2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25699-9https://doaj.org/toc/2045-2322Abstract Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are known to contribute to fibrosis, but less is known about their function during NAFLD’s early stages prior to fibrosis. We developed an ex vivo assay that cocultures primary HSCs from mouse models of liver disease with healthy hepatocytes to study their interaction. Our data indicate that chemokine Ccl5 is one of the HSC-secreted mediators in early NASH in humans and in mice fed with choline-deficient, L-amino acid defined, high fat diet. Furthermore, Ccl5 directly induces steatosis and pro-inflammatory factors in healthy hepatocytes through the receptor Ccr5. Although Ccl5 is already known to be secreted by many liver cell types including HSCs and its pro-fibrotic role well characterized, its pro-steatotic action has not been recognized until now. Similarly, the function of HSCs in fibrogenesis is widely accepted, but their pro-steatotic role has been unclear. Our result suggests that in early NASH, HSCs secrete Ccl5 which contributes to a broad array of mechanisms by which hepatic steatosis and inflammation are achieved.Byeong-Moo KimAhmed Maher AbdelfattahRobin VasanBryan C. FuchsMichael Y. ChoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Byeong-Moo Kim Ahmed Maher Abdelfattah Robin Vasan Bryan C. Fuchs Michael Y. Choi Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
description	Abstract Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are known to contribute to fibrosis, but less is known about their function during NAFLD’s early stages prior to fibrosis. We developed an ex vivo assay that cocultures primary HSCs from mouse models of liver disease with healthy hepatocytes to study their interaction. Our data indicate that chemokine Ccl5 is one of the HSC-secreted mediators in early NASH in humans and in mice fed with choline-deficient, L-amino acid defined, high fat diet. Furthermore, Ccl5 directly induces steatosis and pro-inflammatory factors in healthy hepatocytes through the receptor Ccr5. Although Ccl5 is already known to be secreted by many liver cell types including HSCs and its pro-fibrotic role well characterized, its pro-steatotic action has not been recognized until now. Similarly, the function of HSCs in fibrogenesis is widely accepted, but their pro-steatotic role has been unclear. Our result suggests that in early NASH, HSCs secrete Ccl5 which contributes to a broad array of mechanisms by which hepatic steatosis and inflammation are achieved.
format	article
author	Byeong-Moo Kim Ahmed Maher Abdelfattah Robin Vasan Bryan C. Fuchs Michael Y. Choi
author_facet	Byeong-Moo Kim Ahmed Maher Abdelfattah Robin Vasan Bryan C. Fuchs Michael Y. Choi
author_sort	Byeong-Moo Kim
title	Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
title_short	Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
title_full	Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
title_fullStr	Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
title_full_unstemmed	Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis
title_sort	hepatic stellate cells secrete ccl5 to induce hepatocyte steatosis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e37e7fae676a400cb95ddddefd645c5b
work_keys_str_mv	AT byeongmookim hepaticstellatecellssecreteccl5toinducehepatocytesteatosis AT ahmedmaherabdelfattah hepaticstellatecellssecreteccl5toinducehepatocytesteatosis AT robinvasan hepaticstellatecellssecreteccl5toinducehepatocytesteatosis AT bryancfuchs hepaticstellatecellssecreteccl5toinducehepatocytesteatosis AT michaelychoi hepaticstellatecellssecreteccl5toinducehepatocytesteatosis
_version_	1718384565412691968

Hepatic stellate cells secrete Ccl5 to induce hepatocyte steatosis

Ejemplares similares