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Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium

BACKGROUND: PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characteriz...

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Autores principales: Rao, Rajiv G, Sudhakar, Deepthi, Hogue, Claire P, Amici, Stephanie, Gordon, Lynn K, Braun, Jonathan, Notterpek, Lucia, Goodglick, Lee, Wadehra, Madhuri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110552/
https://www.ncbi.nlm.nih.gov/pubmed/21518455
http://dx.doi.org/10.1186/1477-7827-9-56
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author Rao, Rajiv G
Sudhakar, Deepthi
Hogue, Claire P
Amici, Stephanie
Gordon, Lynn K
Braun, Jonathan
Notterpek, Lucia
Goodglick, Lee
Wadehra, Madhuri
author_facet Rao, Rajiv G
Sudhakar, Deepthi
Hogue, Claire P
Amici, Stephanie
Gordon, Lynn K
Braun, Jonathan
Notterpek, Lucia
Goodglick, Lee
Wadehra, Madhuri
author_sort Rao, Rajiv G
collection PubMed
description BACKGROUND: PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium. METHODS: Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices. RESULTS: In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression. CONCLUSION: These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the maintainence of endometrial integrity and to the disease biology associated with altered levels of α6 integrin expression in the endometrium.
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spelling pubmed-31105522011-06-09 Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium Rao, Rajiv G Sudhakar, Deepthi Hogue, Claire P Amici, Stephanie Gordon, Lynn K Braun, Jonathan Notterpek, Lucia Goodglick, Lee Wadehra, Madhuri Reprod Biol Endocrinol Research BACKGROUND: PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium. METHODS: Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices. RESULTS: In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression. CONCLUSION: These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the maintainence of endometrial integrity and to the disease biology associated with altered levels of α6 integrin expression in the endometrium. BioMed Central 2011-04-25 /pmc/articles/PMC3110552/ /pubmed/21518455 http://dx.doi.org/10.1186/1477-7827-9-56 Text en Copyright ©2011 Rao et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Rao, Rajiv G
Sudhakar, Deepthi
Hogue, Claire P
Amici, Stephanie
Gordon, Lynn K
Braun, Jonathan
Notterpek, Lucia
Goodglick, Lee
Wadehra, Madhuri
Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title_full Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title_fullStr Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title_full_unstemmed Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title_short Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium
title_sort peripheral myelin protein-22 (pmp22) modulates alpha 6 integrin expression in the human endometrium
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110552/
https://www.ncbi.nlm.nih.gov/pubmed/21518455
http://dx.doi.org/10.1186/1477-7827-9-56
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