Emily M Bradford1, Kanimozhi Vairamani1, Gary E Shull1. 1. Emily M Bradford, Department of Internal Medicine, Division of Gastroenterology, University of Kentucky, Lexington, KY 40536-0298, United States.
Abstract
AIM: To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. RESULTS: Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION: The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.
AIM: To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. RESULTS: Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION: The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.
Authors: M Flagella; L L Clarke; M L Miller; L C Erway; R A Giannella; A Andringa; L R Gawenis; J Kramer; J J Duffy; T Doetschman; J N Lorenz; E N Yamoah; E L Cardell; G E Shull Journal: J Biol Chem Date: 1999-09-17 Impact factor: 5.157
Authors: Oliver J Mace; Norma Lister; Emma Morgan; Emma Shepherd; Julie Affleck; Philip Helliwell; John R Bronk; George L Kellett; David Meredith; Richard Boyd; Myrtani Pieri; Pat D Bailey; Rachel Pettcrew; David Foley Journal: J Physiol Date: 2008-11-10 Impact factor: 5.182
Authors: M F Offield; T L Jetton; P A Labosky; M Ray; R W Stein; M A Magnuson; B L Hogan; C V Wright Journal: Development Date: 1996-03 Impact factor: 6.868
Authors: Eric Delpire; Lynne Wolfe; Bianca Flores; Rainelli Koumangoye; Cara C Schornak; Salma Omer; Barbara Pusey; Christopher Lau; Thomas Markello; David R Adams Journal: Cold Spring Harb Mol Case Stud Date: 2016-11
Authors: Kanimozhi Vairamani; Vikram Prasad; Yigang Wang; Wei Huang; Yinhua Chen; Mario Medvedovic; John N Lorenz; Gary E Shull Journal: World J Cardiol Date: 2018-09-26