title: Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
abstract: As a master component of endosomal sorting complex required for transport proteins, hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) participates multiple cellular behaviors. However, the physiological role of Hgs in smooth muscle cells (SMCs) is by far unknown. Here we explored the in vivo function of Hgs in SMCs by using a conditional gene knockout strategy. Hgs deficiency in SMCs uniquely led to a progressive dilatation of esophagus with a remarkable thinning muscle layer. Of note, the mutant esophagus showed a decreased contractile responsiveness to potassium chloride and acetylcholine stimulation. Furthermore, an increase in the inhibitory neurites along with an intense infiltration of T lymphocytes in the mucosa and muscle layer were observed. Consistently, Hgs deficiency in SMCs resulted in a disturbed expression of a set of genes involved in neurotrophin and inflammation, suggesting that defective SMC might be a novel source for excessive production of cytokines and chemokines which may trigger the neuronal dysplasia and ultimately contribute to the compromised esophageal motility. The data suggest potential implications in the pathogenesis of related diseases such as gastroesophageal reflux disease.
authors.affiliation: 1. Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiaotong University, Shanghai 200025, China ; 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Hou
authors.affiliation: 1. Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiaotong University, Shanghai 200025, China ; 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: 3. Department of Cardiovascular Electrophysiology Research, College of Basic Medicine, Capital Medical University, Beijing 100069, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zeng
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: 3. Department of Cardiovascular Electrophysiology Research, College of Basic Medicine, Capital Medical University, Beijing 100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1. Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiaotong University, Shanghai 200025, China ; 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: 2. State Key Laboratory of Proteomics, Collaborative Innovation Center for Cardiovascular Disorders, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D056827:Endosomal Sorting Complexes Required for Transport / Q000172:deficiency*; D015154:Esophageal Motility Disorders / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D016501:Neurites / Q000378:metabolism*; D010750:Phosphoproteins / Q000172:deficiency*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate
keywords: esophageal motility; hepatocyte growth factor-regulated tyrosine kinase substrate; inflammation; inhibitory neurite; smooth muscle cell