Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity

Abstract Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common cli...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ken Lee, Sang O Park, Pil-Cho Choi, Seung-Bum Ryoo, Haeyeong Lee, Lauren E. Peri, Tong Zhou, Robert D. Corrigan, Andrew C. Yanez, Suk B. Moon, Brian A. Perrino, Kenton M. Sanders, Sang Don Koh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ffc5cafa1a74f33afd2860ded277ffe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2ffc5cafa1a74f33afd2860ded277ffe
record_format	dspace
spelling	oai:doaj.org-article:2ffc5cafa1a74f33afd2860ded277ffe2021-12-02T16:43:42ZMolecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity10.1038/s41598-021-95781-22045-2322https://doaj.org/article/2ffc5cafa1a74f33afd2860ded277ffe2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95781-2https://doaj.org/toc/2045-2322Abstract Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.Ken LeeSang O ParkPil-Cho ChoiSeung-Bum RyooHaeyeong LeeLauren E. PeriTong ZhouRobert D. CorriganAndrew C. YanezSuk B. MoonBrian A. PerrinoKenton M. SandersSang Don KohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ken Lee Sang O Park Pil-Cho Choi Seung-Bum Ryoo Haeyeong Lee Lauren E. Peri Tong Zhou Robert D. Corrigan Andrew C. Yanez Suk B. Moon Brian A. Perrino Kenton M. Sanders Sang Don Koh Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
description	Abstract Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.
format	article
author	Ken Lee Sang O Park Pil-Cho Choi Seung-Bum Ryoo Haeyeong Lee Lauren E. Peri Tong Zhou Robert D. Corrigan Andrew C. Yanez Suk B. Moon Brian A. Perrino Kenton M. Sanders Sang Don Koh
author_facet	Ken Lee Sang O Park Pil-Cho Choi Seung-Bum Ryoo Haeyeong Lee Lauren E. Peri Tong Zhou Robert D. Corrigan Andrew C. Yanez Suk B. Moon Brian A. Perrino Kenton M. Sanders Sang Don Koh
author_sort	Ken Lee
title	Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
title_short	Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
title_full	Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
title_fullStr	Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
title_full_unstemmed	Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity
title_sort	molecular and functional characterization of detrusor pdgfrα positive cells in spinal cord injury-induced detrusor overactivity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ffc5cafa1a74f33afd2860ded277ffe
work_keys_str_mv	AT kenlee molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT sangopark molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT pilchochoi molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT seungbumryoo molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT haeyeonglee molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT laureneperi molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT tongzhou molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT robertdcorrigan molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT andrewcyanez molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT sukbmoon molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT brianaperrino molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT kentonmsanders molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity AT sangdonkoh molecularandfunctionalcharacterizationofdetrusorpdgfrapositivecellsinspinalcordinjuryinduceddetrusoroveractivity
_version_	1718383505048600576

Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity

Ejemplares similares