Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation

Summary: Hepatic miRNA, miR-122, plays an important role in controlling metabolic homeostasis in mammalian liver. Intercellular transfer of miR-122 was found to play a role in controlling tissue inflammation. miR-122, as part of extracellular vesicles released by lipid-exposed hepatic cells, are tak...

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Autores principales: Arnab Das, Sudarshana Basu, Diptankar Bandyopadhyay, Kamalika Mukherjee, Debduti Datta, Sreemoyee Chakraborty, Sayantan Jana, Moumita Adak, Sarpita Bose, Saikat Chakrabarti, Snehasikta Swarnakar, Partha Chakrabarti, Suvendra N. Bhattacharyya
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:20ff895894664ecf8a178c647c642da82021-11-28T04:36:18ZInhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation2589-004210.1016/j.isci.2021.103428https://doaj.org/article/20ff895894664ecf8a178c647c642da82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013997https://doaj.org/toc/2589-0042Summary: Hepatic miRNA, miR-122, plays an important role in controlling metabolic homeostasis in mammalian liver. Intercellular transfer of miR-122 was found to play a role in controlling tissue inflammation. miR-122, as part of extracellular vesicles released by lipid-exposed hepatic cells, are taken up by tissue macrophages to activate them and produce inflammatory cytokines. Matrix metalloprotease 2 or MMP2 was found to be essential for transfer of extracellular vesicles and their miRNA content from hepatic to non-hepatic cells. MMP2 was found to increase the movement of the extracellular vesicles along the extracellular matrix to enhance their uptake in recipient cells. Inhibition of MMP2 restricts functional transfer of hepatic miRNAs across the hepatic and non-hepatic cell boundaries, and by targeting MMP2, we could reduce the innate immune response in mammalian liver by preventing intra-tissue miR-122 transfer. MMP2 thus could be a useful target to restrict high-fat-diet-induced obesity-related metaflammation.Arnab DasSudarshana BasuDiptankar BandyopadhyayKamalika MukherjeeDebduti DattaSreemoyee ChakrabortySayantan JanaMoumita AdakSarpita BoseSaikat ChakrabartiSnehasikta SwarnakarPartha ChakrabartiSuvendra N. BhattacharyyaElsevierarticleBiological sciencesMolecular biologyImmunologyScienceQENiScience, Vol 24, Iss 12, Pp 103428- (2021)
institution DOAJ
collection DOAJ
language EN
topic Biological sciences
Molecular biology
Immunology
Science
Q
spellingShingle Biological sciences
Molecular biology
Immunology
Science
Q
Arnab Das
Sudarshana Basu
Diptankar Bandyopadhyay
Kamalika Mukherjee
Debduti Datta
Sreemoyee Chakraborty
Sayantan Jana
Moumita Adak
Sarpita Bose
Saikat Chakrabarti
Snehasikta Swarnakar
Partha Chakrabarti
Suvendra N. Bhattacharyya
Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
description Summary: Hepatic miRNA, miR-122, plays an important role in controlling metabolic homeostasis in mammalian liver. Intercellular transfer of miR-122 was found to play a role in controlling tissue inflammation. miR-122, as part of extracellular vesicles released by lipid-exposed hepatic cells, are taken up by tissue macrophages to activate them and produce inflammatory cytokines. Matrix metalloprotease 2 or MMP2 was found to be essential for transfer of extracellular vesicles and their miRNA content from hepatic to non-hepatic cells. MMP2 was found to increase the movement of the extracellular vesicles along the extracellular matrix to enhance their uptake in recipient cells. Inhibition of MMP2 restricts functional transfer of hepatic miRNAs across the hepatic and non-hepatic cell boundaries, and by targeting MMP2, we could reduce the innate immune response in mammalian liver by preventing intra-tissue miR-122 transfer. MMP2 thus could be a useful target to restrict high-fat-diet-induced obesity-related metaflammation.
format article
author Arnab Das
Sudarshana Basu
Diptankar Bandyopadhyay
Kamalika Mukherjee
Debduti Datta
Sreemoyee Chakraborty
Sayantan Jana
Moumita Adak
Sarpita Bose
Saikat Chakrabarti
Snehasikta Swarnakar
Partha Chakrabarti
Suvendra N. Bhattacharyya
author_facet Arnab Das
Sudarshana Basu
Diptankar Bandyopadhyay
Kamalika Mukherjee
Debduti Datta
Sreemoyee Chakraborty
Sayantan Jana
Moumita Adak
Sarpita Bose
Saikat Chakrabarti
Snehasikta Swarnakar
Partha Chakrabarti
Suvendra N. Bhattacharyya
author_sort Arnab Das
title Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
title_short Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
title_full Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
title_fullStr Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
title_full_unstemmed Inhibition of extracellular vesicle-associated MMP2 abrogates intercellular hepatic miR-122 transfer to liver macrophages and curtails inflammation
title_sort inhibition of extracellular vesicle-associated mmp2 abrogates intercellular hepatic mir-122 transfer to liver macrophages and curtails inflammation
publisher Elsevier
publishDate 2021
url https://doaj.org/article/20ff895894664ecf8a178c647c642da8
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