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Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination

Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of various metalloproteinases including matrix metalloproteinases and ADAM family proteins. In the peripheral nervous system, ADAM17, also known as TNF-α converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type I...

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Autores principales: Kim, Jihyun, Elias, Anthony, Lee, Taeweon, Maurel, Patrice, Kim, Haesun A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718315/
https://www.ncbi.nlm.nih.gov/pubmed/29198135
http://dx.doi.org/10.1177/1759091417745425
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author Kim, Jihyun
Elias, Anthony
Lee, Taeweon
Maurel, Patrice
Kim, Haesun A.
author_facet Kim, Jihyun
Elias, Anthony
Lee, Taeweon
Maurel, Patrice
Kim, Haesun A.
author_sort Kim, Jihyun
collection PubMed
description Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of various metalloproteinases including matrix metalloproteinases and ADAM family proteins. In the peripheral nervous system, ADAM17, also known as TNF-α converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type III, an axonal growth factor that is essential for Schwann cell myelination. The processing by ADAM17 attenuates Nrg1 signaling and inhibits Schwann cell myelination. TIMP-3 targets ADAM17, suggesting a possibility that TIMP-3 may elicit a promyelinating function in Schwann cells by relieving ADAM17-induced myelination block. To investigate this, we used a myelinating coculture system to determine the effect of TIMP-3 on Schwann cell myelination. Treatment with TIMP-3 enhanced myelin formation in cocultures, evident by an increase in the number of myelin segments and upregulated expression of Krox20 and myelin protein. The effect of TIMP-3 was accompanied by the inhibition of ADAM17 activity and an increase in Nrg1 type III signaling in cocultures. Accordingly, the N-terminus fragment of TIMP-3, which exhibits a selective inhibitory function toward ADAM17, elicited a similar myelination-promoting effect and increased Nrg1 type III activity. TIMP-3 also enhanced laminin production in cocultures, which is likely to aid Schwann cell myelination.
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spelling pubmed-57183152017-12-11 Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination Kim, Jihyun Elias, Anthony Lee, Taeweon Maurel, Patrice Kim, Haesun A. ASN Neuro Original Paper Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of various metalloproteinases including matrix metalloproteinases and ADAM family proteins. In the peripheral nervous system, ADAM17, also known as TNF-α converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type III, an axonal growth factor that is essential for Schwann cell myelination. The processing by ADAM17 attenuates Nrg1 signaling and inhibits Schwann cell myelination. TIMP-3 targets ADAM17, suggesting a possibility that TIMP-3 may elicit a promyelinating function in Schwann cells by relieving ADAM17-induced myelination block. To investigate this, we used a myelinating coculture system to determine the effect of TIMP-3 on Schwann cell myelination. Treatment with TIMP-3 enhanced myelin formation in cocultures, evident by an increase in the number of myelin segments and upregulated expression of Krox20 and myelin protein. The effect of TIMP-3 was accompanied by the inhibition of ADAM17 activity and an increase in Nrg1 type III signaling in cocultures. Accordingly, the N-terminus fragment of TIMP-3, which exhibits a selective inhibitory function toward ADAM17, elicited a similar myelination-promoting effect and increased Nrg1 type III activity. TIMP-3 also enhanced laminin production in cocultures, which is likely to aid Schwann cell myelination. SAGE Publications 2017-12-03 /pmc/articles/PMC5718315/ /pubmed/29198135 http://dx.doi.org/10.1177/1759091417745425 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Paper
Kim, Jihyun
Elias, Anthony
Lee, Taeweon
Maurel, Patrice
Kim, Haesun A.
Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title_full Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title_fullStr Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title_full_unstemmed Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title_short Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination
title_sort tissue inhibitor of metalloproteinase-3 promotes schwann cell myelination
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718315/
https://www.ncbi.nlm.nih.gov/pubmed/29198135
http://dx.doi.org/10.1177/1759091417745425
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