Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome

Michael Camilleri, Christopher N. Andrews, Adil Eddie Bharucha, Paula J. Carlson, Irene Ferber, Debra Stephens, Thomas Christopher Smyrk, Raul Urrutia, Jeroen Aerssens, Leen Thielemans, Hinrich Göhlmann, Ilse van den Wyngaert, Bernard Coulie

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background & Aims: 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 ∼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-HT1B 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.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalGastroenterology
Volume132
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Irritable Bowel Syndrome
Biopsy
Serotonin Plasma Membrane Transport Proteins
Sigmoid Colon
Antidepressive Agents
Annexin A2
Receptor, Serotonin, 5-HT1B
Serotonin Agents
Messenger RNA
Proteins
Validation Studies
Serotonin Receptors
Constipation
Rectum
Diarrhea
Serotonin
Carrier Proteins
Mucous Membrane
Genotype
Light

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome. / Camilleri, Michael; Andrews, Christopher N.; Bharucha, Adil Eddie; Carlson, Paula J.; Ferber, Irene; Stephens, Debra; Smyrk, Thomas Christopher; Urrutia, Raul; Aerssens, Jeroen; Thielemans, Leen; Göhlmann, Hinrich; van den Wyngaert, Ilse; Coulie, Bernard.

In: Gastroenterology, Vol. 132, No. 1, 01.2007, p. 17-25.

Research output: Contribution to journalArticle

Camilleri, M, Andrews, CN, Bharucha, AE, Carlson, PJ, Ferber, I, Stephens, D, Smyrk, TC, Urrutia, R, Aerssens, J, Thielemans, L, Göhlmann, H, van den Wyngaert, I & Coulie, B 2007, 'Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome', Gastroenterology, vol. 132, no. 1, pp. 17-25. https://doi.org/10.1053/j.gastro.2006.11.020
Camilleri, Michael ; Andrews, Christopher N. ; Bharucha, Adil Eddie ; Carlson, Paula J. ; Ferber, Irene ; Stephens, Debra ; Smyrk, Thomas Christopher ; Urrutia, Raul ; Aerssens, Jeroen ; Thielemans, Leen ; Göhlmann, Hinrich ; van den Wyngaert, Ilse ; Coulie, Bernard. / Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome. In: Gastroenterology. 2007 ; Vol. 132, No. 1. pp. 17-25.
@article{0faaf386cf2941c4855389fd1c07d88b,
title = "Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome",
abstract = "Background & Aims: 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 ∼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-HT1B 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.",
author = "Michael Camilleri and Andrews, {Christopher N.} and Bharucha, {Adil Eddie} and Carlson, {Paula J.} and Irene Ferber and Debra Stephens and Smyrk, {Thomas Christopher} and Raul Urrutia and Jeroen Aerssens and Leen Thielemans and Hinrich G{\"o}hlmann and {van den Wyngaert}, Ilse and Bernard Coulie",
year = "2007",
month = "1",
doi = "10.1053/j.gastro.2006.11.020",
language = "English (US)",
volume = "132",
pages = "17--25",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - Alterations in Expression of p11 and SERT in Mucosal Biopsy Specimens of Patients With Irritable Bowel Syndrome

AU - Camilleri, Michael

AU - Andrews, Christopher N.

AU - Bharucha, Adil Eddie

AU - Carlson, Paula J.

AU - Ferber, Irene

AU - Stephens, Debra

AU - Smyrk, Thomas Christopher

AU - Urrutia, Raul

AU - Aerssens, Jeroen

AU - Thielemans, Leen

AU - Göhlmann, Hinrich

AU - van den Wyngaert, Ilse

AU - Coulie, Bernard

PY - 2007/1

Y1 - 2007/1

N2 - Background & Aims: 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 ∼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-HT1B 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.

AB - Background & Aims: 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 ∼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-HT1B 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.

UR - http://www.scopus.com/inward/record.url?scp=33846256685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846256685&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2006.11.020

DO - 10.1053/j.gastro.2006.11.020

M3 - Article

C2 - 17241856

AN - SCOPUS:33846256685

VL - 132

SP - 17

EP - 25

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -