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Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis

IC/BPS is a chronic inflammatory pelvic pain syndrome characterized by lower urinary tract symptoms including unpleasant sensation (pain, pressure, or discomfort) in the suprapubic or bladder area, as well as increased urinary frequency and urgency, and decreased bladder capacity. While its etiology...

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Autores principales: Hsiang, Harrison W., Girard, Beatrice M., Vizzard, Margaret A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493645/
https://www.ncbi.nlm.nih.gov/pubmed/37701183
http://dx.doi.org/10.3389/fruro.2022.1089220
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author Hsiang, Harrison W.
Girard, Beatrice M.
Vizzard, Margaret A.
author_facet Hsiang, Harrison W.
Girard, Beatrice M.
Vizzard, Margaret A.
author_sort Hsiang, Harrison W.
collection PubMed
description IC/BPS is a chronic inflammatory pelvic pain syndrome characterized by lower urinary tract symptoms including unpleasant sensation (pain, pressure, or discomfort) in the suprapubic or bladder area, as well as increased urinary frequency and urgency, and decreased bladder capacity. While its etiology remains unknown, increasing evidence suggests a role for changes in nerve growth factor (NGF) signaling. However, NGF signaling is complex and highly context dependent. NGF activates two receptors, TrkA and p75(NTR), which activate distinct but overlapping signaling cascades. Dependent on their coexpression, p75(NTR) facilitates TrkA actions. Here, we show effects of CYP treatment and pharmacological inhibition of p75(NTR) (via LM11A-31) and TrkA (ARRY-954) on NGF signaling–related proteins: NGF, TrkA, phosphorylated (p)-TrkA, p75(NTR), p-ERK1/2, and p-JNK. Cystitis conditions were associated with increased urothelial NGF expression and decreased TrkA and p75(NTR) expression as well as altering their co-expression ratio; phosphorylation of ERK1/2 and JNK were also altered. Both TrkA and p75(NTR) inhibition affected the activation of signaling pathways downstream of TrkA, supporting the hypothesis that NGF actions during cystitis are primarily TrkA-mediated. Our findings, in tandem with our recent companion paper demonstrating the effects of TrkA, TrkB, and p75(NTR) inhibition on bladder function in a mouse model of cystitis, highlight a variety of potent therapeutic targets and provide further insight into the involvement of NGF signaling in sustained conditions of bladder inflammation.
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spelling pubmed-104936452023-09-11 Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis Hsiang, Harrison W. Girard, Beatrice M. Vizzard, Margaret A. Front Urol Article IC/BPS is a chronic inflammatory pelvic pain syndrome characterized by lower urinary tract symptoms including unpleasant sensation (pain, pressure, or discomfort) in the suprapubic or bladder area, as well as increased urinary frequency and urgency, and decreased bladder capacity. While its etiology remains unknown, increasing evidence suggests a role for changes in nerve growth factor (NGF) signaling. However, NGF signaling is complex and highly context dependent. NGF activates two receptors, TrkA and p75(NTR), which activate distinct but overlapping signaling cascades. Dependent on their coexpression, p75(NTR) facilitates TrkA actions. Here, we show effects of CYP treatment and pharmacological inhibition of p75(NTR) (via LM11A-31) and TrkA (ARRY-954) on NGF signaling–related proteins: NGF, TrkA, phosphorylated (p)-TrkA, p75(NTR), p-ERK1/2, and p-JNK. Cystitis conditions were associated with increased urothelial NGF expression and decreased TrkA and p75(NTR) expression as well as altering their co-expression ratio; phosphorylation of ERK1/2 and JNK were also altered. Both TrkA and p75(NTR) inhibition affected the activation of signaling pathways downstream of TrkA, supporting the hypothesis that NGF actions during cystitis are primarily TrkA-mediated. Our findings, in tandem with our recent companion paper demonstrating the effects of TrkA, TrkB, and p75(NTR) inhibition on bladder function in a mouse model of cystitis, highlight a variety of potent therapeutic targets and provide further insight into the involvement of NGF signaling in sustained conditions of bladder inflammation. 2023 2023-01-26 /pmc/articles/PMC10493645/ /pubmed/37701183 http://dx.doi.org/10.3389/fruro.2022.1089220 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Article
Hsiang, Harrison W.
Girard, Beatrice M.
Vizzard, Margaret A.
Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title_full Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title_fullStr Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title_full_unstemmed Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title_short Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
title_sort changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493645/
https://www.ncbi.nlm.nih.gov/pubmed/37701183
http://dx.doi.org/10.3389/fruro.2022.1089220
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