Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth

Abstract We have previously shown myofibroblasts subjacent to the squamous epithelium in the normal human esophagus and an increase in esophagitis. Myofibroblast contribution to bone morphogenetic protein (BMP) signaling and to paracrine mediated epithelial-mesenchymal interactions in the human esop...

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Autores principales:	Chunying Zhang, Chao Niu, Kevin Yang, Anisa Shaker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78ec17605e4045a68cb4d45c46fb9a87
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spelling	oai:doaj.org-article:78ec17605e4045a68cb4d45c46fb9a872021-12-02T15:08:10ZHuman esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth10.1038/s41598-018-30799-72045-2322https://doaj.org/article/78ec17605e4045a68cb4d45c46fb9a872018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30799-7https://doaj.org/toc/2045-2322Abstract We have previously shown myofibroblasts subjacent to the squamous epithelium in the normal human esophagus and an increase in esophagitis. Myofibroblast contribution to bone morphogenetic protein (BMP) signaling and to paracrine mediated epithelial-mesenchymal interactions in the human esophagus remains incompletely defined. We investigated BMP4 and BMP inhibitor GREM1 gene expression and protein levels in previously characterized human esophageal myofibroblast primary cultures and in a human esophageal myofibroblast cell line. We adapted human esophageal myofibroblast conditioned media into a 3D organotypic model to investigate the effect of myofibroblast secreted factors on squamous epithelial morphology, proliferation, differentiation and BMP signaling. Human esophageal myofibroblasts constitutively secrete GREM1 and increase BMP4 expression and BMP4 secretion in response to epithelial Hedgehog ligand SHH. Detection of secreted BMP4 is decreased in the presence of GREM1. Myofibroblast conditioned media increases epithelial proliferation and expression of basal markers p63 and CK14 leading to an overall increase in epithelial thickness. Epithelial BMP signaling increases with myofibroblast conditioned media. These findings were partially reversed with GREM1 inhibition. Our results demonstrate that myofibroblasts are potential sources of GREM1 and of BMP4 in the human esophagus and that human esophageal myofibroblast-epithelial paracrine interactions contribute in part to the regulation of epithelial growth.Chunying ZhangChao NiuKevin YangAnisa ShakerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunying Zhang Chao Niu Kevin Yang Anisa Shaker Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
description	Abstract We have previously shown myofibroblasts subjacent to the squamous epithelium in the normal human esophagus and an increase in esophagitis. Myofibroblast contribution to bone morphogenetic protein (BMP) signaling and to paracrine mediated epithelial-mesenchymal interactions in the human esophagus remains incompletely defined. We investigated BMP4 and BMP inhibitor GREM1 gene expression and protein levels in previously characterized human esophageal myofibroblast primary cultures and in a human esophageal myofibroblast cell line. We adapted human esophageal myofibroblast conditioned media into a 3D organotypic model to investigate the effect of myofibroblast secreted factors on squamous epithelial morphology, proliferation, differentiation and BMP signaling. Human esophageal myofibroblasts constitutively secrete GREM1 and increase BMP4 expression and BMP4 secretion in response to epithelial Hedgehog ligand SHH. Detection of secreted BMP4 is decreased in the presence of GREM1. Myofibroblast conditioned media increases epithelial proliferation and expression of basal markers p63 and CK14 leading to an overall increase in epithelial thickness. Epithelial BMP signaling increases with myofibroblast conditioned media. These findings were partially reversed with GREM1 inhibition. Our results demonstrate that myofibroblasts are potential sources of GREM1 and of BMP4 in the human esophagus and that human esophageal myofibroblast-epithelial paracrine interactions contribute in part to the regulation of epithelial growth.
format	article
author	Chunying Zhang Chao Niu Kevin Yang Anisa Shaker
author_facet	Chunying Zhang Chao Niu Kevin Yang Anisa Shaker
author_sort	Chunying Zhang
title	Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
title_short	Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
title_full	Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
title_fullStr	Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
title_full_unstemmed	Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
title_sort	human esophageal myofibroblast secretion of bone morphogenetic proteins and gremlin1 and paracrine regulation of squamous epithelial growth
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/78ec17605e4045a68cb4d45c46fb9a87
work_keys_str_mv	AT chunyingzhang humanesophagealmyofibroblastsecretionofbonemorphogeneticproteinsandgremlin1andparacrineregulationofsquamousepithelialgrowth AT chaoniu humanesophagealmyofibroblastsecretionofbonemorphogeneticproteinsandgremlin1andparacrineregulationofsquamousepithelialgrowth AT kevinyang humanesophagealmyofibroblastsecretionofbonemorphogeneticproteinsandgremlin1andparacrineregulationofsquamousepithelialgrowth AT anisashaker humanesophagealmyofibroblastsecretionofbonemorphogeneticproteinsandgremlin1andparacrineregulationofsquamousepithelialgrowth
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Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth

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