Project description:The esophagus is a muscular tube which transports swallowed content from the oral cavity and the pharynx to the stomach. Early in mouse development, an entire layer of the esophagus, the muscularis externa, consists of differentiated smooth muscle cells. Starting shortly after mid-gestation till about two weeks after birth, the muscularis externa almost entirely consists of striated muscle. This proximal-to-distal replacement of smooth muscle by the striated muscle depends on a number of factors. To identify the nature of the hypothetical “proximal” (mainly striated muscle originating) and “distal” (mainly smooth muscle originating) signals that govern the striated-for-smooth muscle replacement, we compared the esophagus of Myf5:MyoD null fetuses completely lacking striated muscle to the normal control using cDNA microarray analysis, followed by a comprehensive databases search. Here we provide an insight into the nature of “proximal” and “distal” signals that govern the striated-for-smooth muscle replacement in the esophagus.
Project description:Thiele2013 - Smooth muscle smooth muscle cells
The model of smooth muscle smooth muscle cells metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000
).
This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
.
Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared
with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using
Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic
data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically
generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will
facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110025
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.
Project description:Barrett's esophagus is a metaplastic condition of the distal esophagus, characterized by the replacement of normal squamous epithelium by columnar epithelium. Patients with BE have an increased risk of developing esophageal adenocarcinoma. MicroRNAs have been implicated to be disease and tissue specific, however limited data of microRNA expression in the esophagus is available. Therefore we evaluated microRNA expression profiles of esophageal adenocarcinoma and compared these with Barrett's esophagus and normal squamous esophagus.
Project description:Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in non-contractile tissue and embryonic development has yet to be understood. Tracheobronchomalacia (TBM) and complete tracheal rings (CTR) are disorders affecting the muscle and cartilage of the trachea and bronchi, whose etiology remains poorly understood. We demonstrated that trachealis muscle organization and polarity are disrupted after epithelial ablation of Wls, a cargo receptor critical for the Wnt signaling pathway, in developing trachea. The phenotype resembles the anomalous trachealis muscle observed after deletion of ion channel encoding genes in developing mouse trachea. We sought to investigate whether and how the deletion ofWlsaffects ion channels during tracheal development. We hypothesize that Wnt signaling influences the expression of ion channels to promote trachealis muscle cell assembly and patterning. Deleting Wls in developing trachea causes differential regulation of genes mediating actin binding, cytoskeleton organization, and potassium ion channel activity. Wnt signaling regulated expression of Kcnj13, Kcnd3, Kcnj8, and Abcc9 as demonstrated by in vitro studies and in vivo analysis in Wnt5a and b-catenin deficient tracheas. Pharmacological inhibition of potassium ion channels and Wnt signaling impaired contractility of developing trachealis smooth muscle and formation of cartilaginous mesenchymal condensation. Thus, in mice, epithelial-induced Wnt/b-catenin signaling mediates trachealis muscle and cartilage development via modulation of ion channel expression, promoting trachealis muscle architecture, contractility, and cartilaginous extracellular matrix. In turn, ion channel activity may influence tracheal morphogenesis underlying TBM and CTR.
Project description:Smooth muscle cell TGFβ signaling is one of the primary drivers of smooth muscle cell maturation. Inhibition of smooth muscle cell TGFβ signaling in hyperlipidemic mice induces vessel wall inflammation and vessel wall dilation/dissection and leads aortic aneurysm. We performed bulk RNAseq method to examine smooth muscle cell gene expression profile using fresh human tissues from normal aortic media smooth muscle cells and aneurysm aortic media smooth muscle cells.
Project description:Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
Project description:Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
Project description:Lung smooth muscle cells are including bronchiolar and vascular smooth muscle cells. In order to get adult lung smooth muscle cells, we use transgenic mouse line with smooth muscle actin creERT2, which is a transgenic cre recombinase in Acta2 (contractile smooth muscle cell gene). This mouse line also contains a CAG promoter-driven red fluorescent protein variant (tdTomato) - all inserted into the ROSA26 locus. This mouse line express robust tdTomato fluorescence following cre-mediated recombination after Tamoxifen injection.