The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases

Abstract Tonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that it also modulates immune responses under inflammatory conditions independently of hyperosmol...

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Autores principales:	Hyun Sook Hwang, Mi Hyun Lee, Hyun Ah Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75633f9ad572436bb16d712adbe8d5b5
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spelling	oai:doaj.org-article:75633f9ad572436bb16d712adbe8d5b52021-12-02T16:55:34ZThe TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases10.1038/s41598-021-87813-82045-2322https://doaj.org/article/75633f9ad572436bb16d712adbe8d5b52021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87813-8https://doaj.org/toc/2045-2322Abstract Tonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that it also modulates immune responses under inflammatory conditions independently of hyperosmolality. Fibronectin fragments (FN-fs), which are abundant in the synovial fluid of patients with osteoarthritis (OA), induce expression of matrix metalloproteinases (MMPs) via the toll-like receptor-2 (TLR-2) signaling pathway. In this study we examined whether TonEBP is involved in 29-kDa FN-f-induced expression of MMPs. The expression of TonEBP was significantly higher in human osteoarthritis compared with normal cartilage samples. 29-kDa FN-f affected the expression of MMPs 1, 3, and 13 via TonEBP, and expression and nuclear accumulation of TonEBP were induced by activation of the phospholipase C/NF-κB/MAPK signaling pathway and, in particular, modulated by TLR-2. In addition, 29-kDa FN-f induced the expression of osmoregulatory genes, including Tau-T, SMIT, and AR, as well as voltage-dependent calcium channels via the TonEBP/TLR-2 signaling pathway. These results show that 29-kDa FN-f upregulates MMPs in chondrocytes via the TLR-2/TonEBP signaling pathway.Hyun Sook HwangMi Hyun LeeHyun Ah KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyun Sook Hwang Mi Hyun Lee Hyun Ah Kim The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
description	Abstract Tonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that it also modulates immune responses under inflammatory conditions independently of hyperosmolality. Fibronectin fragments (FN-fs), which are abundant in the synovial fluid of patients with osteoarthritis (OA), induce expression of matrix metalloproteinases (MMPs) via the toll-like receptor-2 (TLR-2) signaling pathway. In this study we examined whether TonEBP is involved in 29-kDa FN-f-induced expression of MMPs. The expression of TonEBP was significantly higher in human osteoarthritis compared with normal cartilage samples. 29-kDa FN-f affected the expression of MMPs 1, 3, and 13 via TonEBP, and expression and nuclear accumulation of TonEBP were induced by activation of the phospholipase C/NF-κB/MAPK signaling pathway and, in particular, modulated by TLR-2. In addition, 29-kDa FN-f induced the expression of osmoregulatory genes, including Tau-T, SMIT, and AR, as well as voltage-dependent calcium channels via the TonEBP/TLR-2 signaling pathway. These results show that 29-kDa FN-f upregulates MMPs in chondrocytes via the TLR-2/TonEBP signaling pathway.
format	article
author	Hyun Sook Hwang Mi Hyun Lee Hyun Ah Kim
author_facet	Hyun Sook Hwang Mi Hyun Lee Hyun Ah Kim
author_sort	Hyun Sook Hwang
title	The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
title_short	The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
title_full	The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
title_fullStr	The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
title_full_unstemmed	The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases
title_sort	tlr-2/tonebp signaling pathway regulates 29-kda fibronectin fragment-dependent expression of matrix metalloproteinases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/75633f9ad572436bb16d712adbe8d5b5
work_keys_str_mv	AT hyunsookhwang thetlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases AT mihyunlee thetlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases AT hyunahkim thetlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases AT hyunsookhwang tlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases AT mihyunlee tlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases AT hyunahkim tlr2tonebpsignalingpathwayregulates29kdafibronectinfragmentdependentexpressionofmatrixmetalloproteinases
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The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases

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