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Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate

Branching morphogenesis is thought to be governed by epithelial-stromal interactions, but the mechanisms underlying specification of branch location remain largely unknown. Prompted by the striking absence of Hedgehog (Hh) response at the sites of nascent buds in regenerating tubules of the adult pr...

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Detalles Bibliográficos
Autores principales: Lim, Agnes, Shin, Kunyoo, Zhao, Chen, Kawano, Sally, Beachy, Philip A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327780/
https://www.ncbi.nlm.nih.gov/pubmed/25362352
http://dx.doi.org/10.1038/ncb3057
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author Lim, Agnes
Shin, Kunyoo
Zhao, Chen
Kawano, Sally
Beachy, Philip A.
author_facet Lim, Agnes
Shin, Kunyoo
Zhao, Chen
Kawano, Sally
Beachy, Philip A.
author_sort Lim, Agnes
collection PubMed
description Branching morphogenesis is thought to be governed by epithelial-stromal interactions, but the mechanisms underlying specification of branch location remain largely unknown. Prompted by the striking absence of Hedgehog (Hh) response at the sites of nascent buds in regenerating tubules of the adult prostate, we investigated the role of Hh signaling in adult prostate branching morphogenesis. We find that pathway activity is localized to stromal cells, and that its attenuation by genetic or pharmacologic manipulation leads to increased branching. Decreased pathway activity correlates with increased stromal production of Hepatocyte growth factor (Hgf), and we show that Hgf induces epithelial tubule branching. Regulation of Hgf expression by Hh signaling is indirect, mediated by Hh-induced expression of microRNAs miR-26a and miR-26b, which in turn down-regulate expression of Hgf. Prostate tubule branching thus may be initiated from regions of low Hh pathway activity, with implications for the prostatic hyperplasia commonly observed in late adulthood.
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spelling pubmed-43277802015-06-01 Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate Lim, Agnes Shin, Kunyoo Zhao, Chen Kawano, Sally Beachy, Philip A. Nat Cell Biol Article Branching morphogenesis is thought to be governed by epithelial-stromal interactions, but the mechanisms underlying specification of branch location remain largely unknown. Prompted by the striking absence of Hedgehog (Hh) response at the sites of nascent buds in regenerating tubules of the adult prostate, we investigated the role of Hh signaling in adult prostate branching morphogenesis. We find that pathway activity is localized to stromal cells, and that its attenuation by genetic or pharmacologic manipulation leads to increased branching. Decreased pathway activity correlates with increased stromal production of Hepatocyte growth factor (Hgf), and we show that Hgf induces epithelial tubule branching. Regulation of Hgf expression by Hh signaling is indirect, mediated by Hh-induced expression of microRNAs miR-26a and miR-26b, which in turn down-regulate expression of Hgf. Prostate tubule branching thus may be initiated from regions of low Hh pathway activity, with implications for the prostatic hyperplasia commonly observed in late adulthood. 2014-11-02 2014-12 /pmc/articles/PMC4327780/ /pubmed/25362352 http://dx.doi.org/10.1038/ncb3057 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lim, Agnes
Shin, Kunyoo
Zhao, Chen
Kawano, Sally
Beachy, Philip A.
Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title_full Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title_fullStr Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title_full_unstemmed Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title_short Spatially restricted Hedgehog signaling regulates HGF-induced branching of the adult prostate
title_sort spatially restricted hedgehog signaling regulates hgf-induced branching of the adult prostate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327780/
https://www.ncbi.nlm.nih.gov/pubmed/25362352
http://dx.doi.org/10.1038/ncb3057
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