Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis

We report that K5.Smad7 mice, which express Smad7 transgene by a keratin-5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to NF-κB activation known to contribute to oral mucositis, we found activated TGF-β signaling in oral mucositis. Smad7 dampe...

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Main Authors:	Han, Gangwen, Bian, Li, Li, Fulun, Cotrim, Ana, Wang, Donna, Lu, Jian Bo, Deng, Yu, Bird, Gregory, Sowers, Anastasia, Mitchell, James B., Gutkind, J. Silvio, Zhao, Rui, Raben, David, Dijke, Peter ten, Refaeli, Yosef, Zhang, Qinghong, Wang, Xiao-Jing
Format:	Online
Language:	English
Published:	2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780964/

id	pubmed-3780964
recordtype	oai_dc
spelling	pubmed-37809642013-10-01 Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis Han, Gangwen Bian, Li Li, Fulun Cotrim, Ana Wang, Donna Lu, Jian Bo Deng, Yu Bird, Gregory Sowers, Anastasia Mitchell, James B. Gutkind, J. Silvio Zhao, Rui Raben, David Dijke, Peter ten Refaeli, Yosef Zhang, Qinghong Wang, Xiao-Jing Article We report that K5.Smad7 mice, which express Smad7 transgene by a keratin-5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to NF-κB activation known to contribute to oral mucositis, we found activated TGF-β signaling in oral mucositis. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-β signaling Smads and their co-repressor CtBP1 transcriptionally repressed Rac1, and Smad7 abrogated this repression. Knocking down Rac1 in mouse keratinocytes abrogated Smad7-induced migration. Topically applying Smad7 protein with a cell permeable Tat-tag (Tat-Smad7) to oral mucosa showed preventive and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified novel molecular mechanisms involved in oral mucositis pathogenesis and our data suggest an alternative therapeutic strategy to block multiple pathological processes of oral mucositis. 2013-03-10 2013-04 /pmc/articles/PMC3780964/ /pubmed/23475202 http://dx.doi.org/10.1038/nm.3118 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
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	Han, Gangwen Bian, Li Li, Fulun Cotrim, Ana Wang, Donna Lu, Jian Bo Deng, Yu Bird, Gregory Sowers, Anastasia Mitchell, James B. Gutkind, J. Silvio Zhao, Rui Raben, David Dijke, Peter ten Refaeli, Yosef Zhang, Qinghong Wang, Xiao-Jing
spellingShingle	Han, Gangwen Bian, Li Li, Fulun Cotrim, Ana Wang, Donna Lu, Jian Bo Deng, Yu Bird, Gregory Sowers, Anastasia Mitchell, James B. Gutkind, J. Silvio Zhao, Rui Raben, David Dijke, Peter ten Refaeli, Yosef Zhang, Qinghong Wang, Xiao-Jing Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
author_facet	Han, Gangwen Bian, Li Li, Fulun Cotrim, Ana Wang, Donna Lu, Jian Bo Deng, Yu Bird, Gregory Sowers, Anastasia Mitchell, James B. Gutkind, J. Silvio Zhao, Rui Raben, David Dijke, Peter ten Refaeli, Yosef Zhang, Qinghong Wang, Xiao-Jing
author_sort	Han, Gangwen
title	Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
title_short	Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
title_full	Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
title_fullStr	Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
title_full_unstemmed	Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis
title_sort	preventive and therapeutic effects of smad7 on radiation-induced oral mucositis
description	We report that K5.Smad7 mice, which express Smad7 transgene by a keratin-5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to NF-κB activation known to contribute to oral mucositis, we found activated TGF-β signaling in oral mucositis. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-β signaling Smads and their co-repressor CtBP1 transcriptionally repressed Rac1, and Smad7 abrogated this repression. Knocking down Rac1 in mouse keratinocytes abrogated Smad7-induced migration. Topically applying Smad7 protein with a cell permeable Tat-tag (Tat-Smad7) to oral mucosa showed preventive and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified novel molecular mechanisms involved in oral mucositis pathogenesis and our data suggest an alternative therapeutic strategy to block multiple pathological processes of oral mucositis.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780964/
_version_	1612013595176992768

Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis

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