Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-10-10
pubmed:abstractText
To understand whether extracellular calcium-sensing receptor (CaSR) expression on colonic myofibroblast cells (18Co) contributed to epithelial homeostasis, we activated the CaSR with 5 mM Ca(2+), screened by RT-PCR Wnt family members, and measured their secretion. Transcripts for Wnt 1, 2, 2b, 3a, 4, and 7a were either absent or unchanged whereas Wnt3 decreased and Wnt5a increased. We assessed Wnt5a secretion by Western blot. High Ca(2+) (5 mM) substantially increased Wnt5a secretion; small interfering RNA (siRNA) against the CaSR reduced this to constitutive amounts. Expression of Wnt5a plasmid but not Wnt1 or Wnt3a increased caudal homeodomain factor CDX2 transcripts and protein in HT-29 adenocarcinoma cells. Wnt5a increased activity of a sucrase-isomaltase (SI) promoter in Caco-2BBE cells. Wnt5a protein stimulation of CDX2 transcripts and protein and SI reporter were increased by overexpression of wild-type Ror2, a Wnt5a receptor, and reduced with siRNA against Ror2. CaSR activation of HT-29 cells increased Ror2 protein expression. Ror2 protein was expressed in mouse jejunum from crypt base to villus tip and in the colon on surface epithelia. Our results show that activation of a G protein-coupled receptor, the CaSR, stimulates secretion of Wnt5a from myofibroblasts. Stimulation of epithelia by the CaSR increased the expression of a receptor for Wnt5a, the tyrosine kinase Ror2, suggesting existence of a unique paracrine relationship for CDX2 homoeostasis in the intestine and revealing new contributions of CaSR-activated myofibroblasts to intestinal stem cell niche microenvironments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CASR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDX2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ROR2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Receptor Tyrosine Kinase-like..., http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcium-Sensing, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Sucrase-Isomaltase Complex, http://linkedlifedata.com/resource/pubmed/chemical/WNT5A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G748-59
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia.
pubmed:affiliation
Department of Physiology, Queen's University, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't