Cargando…

Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation

Eviprostat is a popular phytotherapeutic agent for the treatment of lower urinary tract symptoms (LUTS). At present, the signaling mechanisms underlying its therapeutic effects are still poorly understood. Given that cAMP has been reported to suppress cell hyperplasia and hypertrophy in various path...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Kai, Yao, Jian, Chi, Yuan, Sawada, Norifumi, Araki, Isao, Kitamura, Masanori, Takeda, Masayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709776/
https://www.ncbi.nlm.nih.gov/pubmed/23743824
http://dx.doi.org/10.3390/ijms140612107
_version_ 1782276800886341632
author Li, Kai
Yao, Jian
Chi, Yuan
Sawada, Norifumi
Araki, Isao
Kitamura, Masanori
Takeda, Masayuki
author_facet Li, Kai
Yao, Jian
Chi, Yuan
Sawada, Norifumi
Araki, Isao
Kitamura, Masanori
Takeda, Masayuki
author_sort Li, Kai
collection PubMed
description Eviprostat is a popular phytotherapeutic agent for the treatment of lower urinary tract symptoms (LUTS). At present, the signaling mechanisms underlying its therapeutic effects are still poorly understood. Given that cAMP has been reported to suppress cell hyperplasia and hypertrophy in various pathological situations, we asked whether the effect of Eviprostat could be ascribed to the activation of the cAMP signaling pathway. In the study, exposure of cAMP response element (CRE)-secreted alkaline phosphatase (SEAP) (CRE-SEAP)-reporter cells to Eviprostat elevated SEAP secretion, which was associated with an increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and cAMP-response element-binding protein (CREB), as well as enhanced expression of CRE-regulated protein connexin43, indicating an activation of the cAMP signaling pathway. Consistent with these observations, Eviprostat-induced expression of Cx43 was abolished in the presence of adenylyl cyclase inhibitor SQ22536 or PKA inhibitor H89, whereas it was mimicked by adenylyl cyclase activator, forskolin. Further analysis demonstrated that Eviprostat significantly potentiated the effect of phosphodiesterase 3 (PDE3) inhibitor, but not that of PDE4 inhibitor, on CRE activation. Moreover, Eviprostat suppressed PDGF-induced activation of ERK and Akt and inhibited cell proliferation and hillock formation in both mesangial cells and bladder smooth muscle cells. Collectively, activation of the cAMP signaling pathway could be an important mechanism by which Eviprostat exerts its therapeutic effects for LUTS.
format Online
Article
Text
id pubmed-3709776
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-37097762013-07-12 Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation Li, Kai Yao, Jian Chi, Yuan Sawada, Norifumi Araki, Isao Kitamura, Masanori Takeda, Masayuki Int J Mol Sci Article Eviprostat is a popular phytotherapeutic agent for the treatment of lower urinary tract symptoms (LUTS). At present, the signaling mechanisms underlying its therapeutic effects are still poorly understood. Given that cAMP has been reported to suppress cell hyperplasia and hypertrophy in various pathological situations, we asked whether the effect of Eviprostat could be ascribed to the activation of the cAMP signaling pathway. In the study, exposure of cAMP response element (CRE)-secreted alkaline phosphatase (SEAP) (CRE-SEAP)-reporter cells to Eviprostat elevated SEAP secretion, which was associated with an increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and cAMP-response element-binding protein (CREB), as well as enhanced expression of CRE-regulated protein connexin43, indicating an activation of the cAMP signaling pathway. Consistent with these observations, Eviprostat-induced expression of Cx43 was abolished in the presence of adenylyl cyclase inhibitor SQ22536 or PKA inhibitor H89, whereas it was mimicked by adenylyl cyclase activator, forskolin. Further analysis demonstrated that Eviprostat significantly potentiated the effect of phosphodiesterase 3 (PDE3) inhibitor, but not that of PDE4 inhibitor, on CRE activation. Moreover, Eviprostat suppressed PDGF-induced activation of ERK and Akt and inhibited cell proliferation and hillock formation in both mesangial cells and bladder smooth muscle cells. Collectively, activation of the cAMP signaling pathway could be an important mechanism by which Eviprostat exerts its therapeutic effects for LUTS. Molecular Diversity Preservation International (MDPI) 2013-06-06 /pmc/articles/PMC3709776/ /pubmed/23743824 http://dx.doi.org/10.3390/ijms140612107 Text en © 2013 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Li, Kai
Yao, Jian
Chi, Yuan
Sawada, Norifumi
Araki, Isao
Kitamura, Masanori
Takeda, Masayuki
Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title_full Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title_fullStr Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title_full_unstemmed Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title_short Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation
title_sort eviprostat activates camp signaling pathway and suppresses bladder smooth muscle cell proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709776/
https://www.ncbi.nlm.nih.gov/pubmed/23743824
http://dx.doi.org/10.3390/ijms140612107
work_keys_str_mv AT likai eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT yaojian eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT chiyuan eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT sawadanorifumi eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT arakiisao eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT kitamuramasanori eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation
AT takedamasayuki eviprostatactivatescampsignalingpathwayandsuppressesbladdersmoothmusclecellproliferation