Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome.
OBJECTIVE
The pathophysiology of irritable bowel syndrome (IBS) remains enigmatic; abnormalities in serotonin metabolism have been implicated. Two proteins that influence the function of serotonin and serotonergic receptors are serotonin transporter protein (SERT or soluble carrier protein, SLC6A4) and p11 (S-100A10, or calpactin I light chain). Both proteins are reported to be associated with depression-like states, a frequent comorbid condition in IBS. We explored the hypothesis that expression of these 2 proteins in colonic and rectal mucosa is abnormal in patients with IBS as compared with healthy controls.


METHODS
Messenger RNA (mRNA) expression of SLC6A4 and p11 was measured in sigmoid and rectal mucosal biopsy specimens. Genotype of the promoter for SLC6A4 was also assessed in all participants. Validation studies explored reproducibility of 2 biopsy specimens taken from the same region and biopsy specimens taken an average of approximately 3 months apart.


RESULTS
We found normal colonic mucosal expression of SLC6A4 in diarrhea (IBS-D)- or constipation-predominant IBS (IBS-C). On the other hand, p11 expression was increased in IBS. No significant effect on p11 mRNA expression in sigmoid colon or rectum was noted from antidepressant treatment in any of the analyzed subgroups.


CONCLUSIONS
Colonic mucosal expression of SLC6A4 in IBS is normal. Given that overexpression of p11 can increase serotonergic receptor functions (eg, 5-HT(1B) receptors), these data support the need for further study of the interaction between p11 expression in health and disease and its role in the therapeutic response to serotonergic agents, including antidepressants.
Camilleri
Michael
M
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Group and Gastroenterology Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
Andrews
Christopher N
CN
Bharucha
Adil E
AE
Carlson
Paula J
PJ
Ferber
Irene
I
Stephens
Debra
D
Smyrk
Thomas C
TC
Urrutia
Raul
R
Aerssens
Jeroen
J
Thielemans
Leen
L
Göhlmann
Hinrich
H
van den Wyngaert
Ilse
I
Coulie
Bernard
B
D000328:Adult; D000368:Aged; D017306:Annexin A2 / Q000235:genetics*; D001706:Biopsy / Q000379:methods / Q000592:standards*; D003106:Colon / Q000473:pathology / Q000502:physiology; D003248:Constipation / Q000473:pathology / Q000503:physiopathology; D003967:Diarrhea / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology; D043183:Irritable Bowel Syndrome / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012007:Rectum / Q000473:pathology / Q000502:physiology; D015203:Reproducibility of Results; D009418:S100 Proteins / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D012333:RNA, Messenger; D009418:S100 Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D000099248:S100 Calcium Binding Protein A10; C493230:SLC6A4 protein, human