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AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant h...

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Autores principales: Lee, Saerom, Lim, Ga-Eun, Kim, Yong-Nyun, Koo, Hyeon-Sook, Shim, Jaegal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915421/
https://www.ncbi.nlm.nih.gov/pubmed/33561975
http://dx.doi.org/10.3390/ijms22041639
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author Lee, Saerom
Lim, Ga-Eun
Kim, Yong-Nyun
Koo, Hyeon-Sook
Shim, Jaegal
author_facet Lee, Saerom
Lim, Ga-Eun
Kim, Yong-Nyun
Koo, Hyeon-Sook
Shim, Jaegal
author_sort Lee, Saerom
collection PubMed
description The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.
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spelling pubmed-79154212021-03-01 AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression Lee, Saerom Lim, Ga-Eun Kim, Yong-Nyun Koo, Hyeon-Sook Shim, Jaegal Int J Mol Sci Article The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions. MDPI 2021-02-06 /pmc/articles/PMC7915421/ /pubmed/33561975 http://dx.doi.org/10.3390/ijms22041639 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Saerom
Lim, Ga-Eun
Kim, Yong-Nyun
Koo, Hyeon-Sook
Shim, Jaegal
AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title_full AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title_fullStr AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title_full_unstemmed AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title_short AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression
title_sort ap2m1 supports tgf-β signals to promote collagen expression by inhibiting caveolin expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915421/
https://www.ncbi.nlm.nih.gov/pubmed/33561975
http://dx.doi.org/10.3390/ijms22041639
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