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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4327780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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