Targeting miR-155 to Treat Experimental Scleroderma

Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, an...

Full description

Bibliographic Details
Main Authors:	Yan, Qingran, Chen, Jie, Li, Wei, Bao, Chunde, Fu, Qiong
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734331/

id	pubmed-4734331
recordtype	oai_dc
spelling	pubmed-47343312016-02-05 Targeting miR-155 to Treat Experimental Scleroderma Yan, Qingran Chen, Jie Li, Wei Bao, Chunde Fu, Qiong Article Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155−/− mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications. Nature Publishing Group 2016-02-01 /pmc/articles/PMC4734331/ /pubmed/26828700 http://dx.doi.org/10.1038/srep20314 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yan, Qingran Chen, Jie Li, Wei Bao, Chunde Fu, Qiong
spellingShingle	Yan, Qingran Chen, Jie Li, Wei Bao, Chunde Fu, Qiong Targeting miR-155 to Treat Experimental Scleroderma
author_facet	Yan, Qingran Chen, Jie Li, Wei Bao, Chunde Fu, Qiong
author_sort	Yan, Qingran
title	Targeting miR-155 to Treat Experimental Scleroderma
title_short	Targeting miR-155 to Treat Experimental Scleroderma
title_full	Targeting miR-155 to Treat Experimental Scleroderma
title_fullStr	Targeting miR-155 to Treat Experimental Scleroderma
title_full_unstemmed	Targeting miR-155 to Treat Experimental Scleroderma
title_sort	targeting mir-155 to treat experimental scleroderma
description	Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155−/− mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734331/
_version_	1613530988178046976

Targeting miR-155 to Treat Experimental Scleroderma

Similar Items