PMID- 24819541 OWN - NLM STAT- MEDLINE DCOM- 20150331 LR - 20161125 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 53 DP - 2014 Aug TI - PTEN in smooth muscle cells is essential for colonic immune homeostasis. PG - 108-14 LID - S1357-2725(14)00145-9 [pii] LID - 10.1016/j.biocel.2014.04.029 [doi] AB - Colonic immune homeostasis is essential for normal gastrointestinal tract functioning. In this study, we report that specific gene targeting of phosphatase and tensin homolog (PTEN) in smooth muscle cells caused age-related colonic lymphoid hyperplasia followed by global immune activation in mice. Beginning at 5 weeks of age, these mutant mice displayed massive neutrophil infiltration in the colonic lamina propria. The gene expression levels of pro-inflammatory cytokines and chemokines, including those code for monocyte chemotactic protein-1 (Mcp-1), stromal cell-derived factor 1alpha (Sdf-1alpha), and chemokine (C-C motif) ligand 28 (Ccl-28), were upregulated in the colon. Accordingly, permeability and proliferation of the colonic epithelium was compromised. These abnormalities were alleviated to a great extent when the mutants were crossed with Akt1-null mice, indicating that the pathogenesis was mediated by Akt1 signaling. Our results suggest that in smooth muscle cells, PTEN is crucial for maintaining colonic immune homeostasis. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Qi, Xin AU - Qi X AD - Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Nanjing 210061, China. FAU - Xu, Jingyue AU - Xu J AD - Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China. FAU - Gu, Pengyu AU - Gu P AD - Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China. FAU - Yang, Xiao AU - Yang X AD - Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, PR China. FAU - Gao, Xiang AU - Gao X AD - MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Nanjing 210061, China. Electronic address: gaoxiang@nju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140510 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL12) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (Pten protein, mouse) SB - IM MH - Animals MH - Chemokine CCL2/biosynthesis MH - Chemokine CXCL12/biosynthesis MH - Colonic Neoplasms/*genetics/immunology/pathology MH - Gene Expression Regulation, Neoplastic MH - Inflammation/*genetics/immunology/pathology MH - Mice MH - Myocytes, Smooth Muscle/immunology/metabolism/pathology MH - Neutrophils/immunology/pathology MH - PTEN Phosphohydrolase/*genetics/metabolism MH - Proto-Oncogene Proteins c-akt/genetics MH - Pseudolymphoma/*genetics/pathology MH - Signal Transduction/genetics OTO - NOTNLM OT - Akt1 OT - Immune activation OT - Lymphoid follicle OT - PTEN OT - Smooth muscle cell EDAT- 2014/05/14 06:00 MHDA- 2015/04/01 06:00 CRDT- 2014/05/14 06:00 PHST- 2013/11/25 00:00 [received] PHST- 2014/04/14 00:00 [revised] PHST- 2014/04/29 00:00 [accepted] PHST- 2014/05/14 06:00 [entrez] PHST- 2014/05/14 06:00 [pubmed] PHST- 2015/04/01 06:00 [medline] AID - S1357-2725(14)00145-9 [pii] AID - 10.1016/j.biocel.2014.04.029 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2014 Aug;53:108-14. doi: 10.1016/j.biocel.2014.04.029. Epub 2014 May 10.