dc.contributor.author |
Peiris, Dinithi |
|
dc.contributor.author |
Pacheco, Ivan |
|
dc.contributor.author |
Spencer, Craig |
|
dc.contributor.author |
MacLeod, R. John |
|
dc.date.accessioned |
2016-12-01T05:57:30Z |
|
dc.date.available |
2016-12-01T05:57:30Z |
|
dc.date.issued |
2006-11-30 |
|
dc.identifier.citation |
Peiris, D., Pacheco, I., Spencer, C., & MacLeod, R.J. (2006). The Extracellular Calcium-Sensing Receptor Reciprocally Regulates the Secretion of BMP-2 and the BMP Antagonist Noggin in Colonic Myofibroblasts. Am J Physiol Gastrointest Liver Physiol 292, G753–G766. doi: 10.1152/ajpgi.00225.2006 |
en_US, si_LK |
dc.identifier.uri |
http://dr.lib.sjp.ac.lk/handle/123456789/3493 |
|
dc.description.abstract |
Attached |
en_US, si_LK |
dc.description.abstract |
To understand whether postprandial extracellular Ca(2+) (Ca(o)(2+)) changes were related to intestinal epithelial homeostasis, we performed array analysis on extracellular calcium-sensing receptor (CaSR)-expressing colonic myofibroblasts (18Co cells) and observed increases in bone morphogenetic protein (BMP)-2 transcripts. The present experiments demonstrated that regulated secretion of BMP-2 occurs in response to CaSR activation of these cells and revealed a new property of BMP-2 on the intestinal barrier. Activation by Ca(o)(2+), spermine, GdCl(3), or neomycin sulfate of 18Co cells or primary isolates of myofibroblasts from the normal human colon stimulated both the synthesis (RT-PCR) and secretion (ELISA) of BMP-2. Transient transfection with short interfering RNA against CaSR completely inhibited BMP-2 secretion. Transient transfection with dominant negative CaSR (R185Q) increased the EC(50) of Ca(o)(2+) (5.7 vs. 2.3 mM). Upregulation of BMP-2 transcript and secretion occurring within 3 h of CaSR activation was prevented by actinomycin D. CaSR-mediated BMP-2 synthesis and secretion required phosphatidylinositol 3-kinase activation (as assessed by phospho-Akt generation). Exogenous BMP-2 and conditioned medium from CaSR-stimulated 18Co cells accelerated restitution in wounded postconfluent Caco-2 cells. Exogenous BMP-2 and conditioned medium from CaSR-stimulated 18Co cells increased the transepithelial resistance of low- and high-resistance T-84 epithelial monolayers. CaSR stimulation of T-84 epithelia and colonic myofibroblasts downregulated the BMP family antagonist Noggin, as assessed by RT-PCR and Western blot analysis. Together, our data suggest that the CaSR mediates the effective concentration of BMP-2 in the intestine, which leads to enhanced repair and barrier development. |
|
dc.language.iso |
en |
en_US, si_LK |
dc.publisher |
The American Physiological Society |
en_US, si_LK |
dc.relation.ispartofseries |
doi:10.1152/ajpgi.00225.2006; |
|
dc.title |
The extracellular calcium-sensing receptor reciprocally regulates the secretion of BMP-2 and the BMP antagonist Noggin in colonic myofibroblasts |
en_US, si_LK |
dc.type |
Article |
en_US, si_LK |