Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction

Milk fat globule-EGF factor 8 (MFG-E8) protein is known as an immunomodulator in various diseases, and we previously demonstrated the anti-fibrotic role of MFG-E8 in liver disease. Here, we present a truncated form of MFG-E8 that provides an advanced therapeutic benefit in treating liver fibrosis. T...

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Autores principales:	Geun Ho An, Jaehun Lee, Xiong Jin, Jinwoo Chung, Joon-Chul Kim, Jung-Hyuck Park, Minkyung Kim, Choongseong Han, Jong-Hoon Kim, Dong-Hun Woo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	liver fibrosis liver disease protein therapy integrin TGF-β Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/570bd1297cf04521a6bc3049adc0ebde
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spelling	oai:doaj.org-article:570bd1297cf04521a6bc3049adc0ebde2021-11-25T16:48:37ZTruncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction10.3390/biomedicines91115292227-9059https://doaj.org/article/570bd1297cf04521a6bc3049adc0ebde2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1529https://doaj.org/toc/2227-9059Milk fat globule-EGF factor 8 (MFG-E8) protein is known as an immunomodulator in various diseases, and we previously demonstrated the anti-fibrotic role of MFG-E8 in liver disease. Here, we present a truncated form of MFG-E8 that provides an advanced therapeutic benefit in treating liver fibrosis. The enhanced therapeutic potential of the modified MFG-E8 was demonstrated in various liver fibrosis animal models, and the efficacy was further confirmed in human hepatic stellate cells and a liver spheroid model. In the subsequent analysis, we found that the modified MFG-E8 more efficiently suppressed transforming growth factor β (TGF-β) signaling than the original form of MFG-E8, and it deactivated the proliferation of hepatic stellate cells in the liver disease environment through interfering with the interactions between integrins (αvβ3 & αvβ5) and TGF-βRI. Furthermore, the protein preferentially delivered in the liver after administration, and the safety profiles of the protein were demonstrated in male and female rat models. Therefore, in conclusion, this modified MFG-E8 provides a promising new therapeutic strategy for treating fibrotic diseases.Geun Ho AnJaehun LeeXiong JinJinwoo ChungJoon-Chul KimJung-Hyuck ParkMinkyung KimChoongseong HanJong-Hoon KimDong-Hun WooMDPI AGarticleliver fibrosisliver diseaseprotein therapyintegrinTGF-βBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1529, p 1529 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver fibrosis liver disease protein therapy integrin TGF-β Biology (General) QH301-705.5
spellingShingle	liver fibrosis liver disease protein therapy integrin TGF-β Biology (General) QH301-705.5 Geun Ho An Jaehun Lee Xiong Jin Jinwoo Chung Joon-Chul Kim Jung-Hyuck Park Minkyung Kim Choongseong Han Jong-Hoon Kim Dong-Hun Woo Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
description	Milk fat globule-EGF factor 8 (MFG-E8) protein is known as an immunomodulator in various diseases, and we previously demonstrated the anti-fibrotic role of MFG-E8 in liver disease. Here, we present a truncated form of MFG-E8 that provides an advanced therapeutic benefit in treating liver fibrosis. The enhanced therapeutic potential of the modified MFG-E8 was demonstrated in various liver fibrosis animal models, and the efficacy was further confirmed in human hepatic stellate cells and a liver spheroid model. In the subsequent analysis, we found that the modified MFG-E8 more efficiently suppressed transforming growth factor β (TGF-β) signaling than the original form of MFG-E8, and it deactivated the proliferation of hepatic stellate cells in the liver disease environment through interfering with the interactions between integrins (αvβ3 & αvβ5) and TGF-βRI. Furthermore, the protein preferentially delivered in the liver after administration, and the safety profiles of the protein were demonstrated in male and female rat models. Therefore, in conclusion, this modified MFG-E8 provides a promising new therapeutic strategy for treating fibrotic diseases.
format	article
author	Geun Ho An Jaehun Lee Xiong Jin Jinwoo Chung Joon-Chul Kim Jung-Hyuck Park Minkyung Kim Choongseong Han Jong-Hoon Kim Dong-Hun Woo
author_facet	Geun Ho An Jaehun Lee Xiong Jin Jinwoo Chung Joon-Chul Kim Jung-Hyuck Park Minkyung Kim Choongseong Han Jong-Hoon Kim Dong-Hun Woo
author_sort	Geun Ho An
title	Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
title_short	Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
title_full	Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
title_fullStr	Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
title_full_unstemmed	Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction
title_sort	truncated milk fat globule-egf-like factor 8 ameliorates liver fibrosis via inhibition of integrin-tgfβ receptor interaction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/570bd1297cf04521a6bc3049adc0ebde
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Truncated Milk Fat Globule-EGF-like Factor 8 Ameliorates Liver Fibrosis via Inhibition of Integrin-TGFβ Receptor Interaction

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