Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2018; 24(7): 775-793
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.775
Glucose transporter expression in the human colon
Flavia Merigo, Alessandro Brandolese, Sonia Facchin, Silvia Missaggia, Paolo Bernardi, Federico Boschi, Renata D’Incà, Edoardo Vincenzo Savarino, Andrea Sbarbati, Giacomo Carlo Sturniolo
Flavia Merigo, Silvia Missaggia, Paolo Bernardi, Andrea Sbarbati, Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona I-37134, Italy
Alessandro Brandolese, Department of Medicine, Gastroenterology Section, University of Verona, Verona I-37134, Italy
Sonia Facchin, Renata D’Incà, Edoardo Vincenzo Savarino, Giacomo Carlo Sturniolo, Department of Surgery, Oncology and Gastroenterology, Gastroenterology Section, University Hospital of Padua, Padua I-35128, Italy
Federico Boschi, Department of Computer Science, University of Verona, Verona I-37134, Italy
Author contributions: Merigo F was involved in experimental design, immunohistochemistry, data analyses, and manuscript writing; Brandolese A contributed to clinical sample documentation, presentation of the results, and manuscript writing; Facchin S, D’Incà R and Savarino EV contributed to clinical sample collection and documentation; Missaggia S contributed to immunohistochemistry analysis; Bernardi P performed SEM analysis; Boschi F analyzed the data; Sbarbati A and Sturniolo GC were involved in experimental design, final critical reading of the manuscript before submission; all authors contributed to the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Padua University Hospital (study n° 2813P) Institutional Review Board.
Conflict-of-interest statement: All authors declare no conflicts of interest.
Data sharing statement: Technical appendix and data set are available from the corresponding author at flavia.merigo@univr.it. Participants gave informed consent for data sharing. The present data are anonymized and the risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Flavia Merigo, BSc, Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine and Movement, University of Verona, Strada Le Grazie 8, Verona I-37134, Italy. flavia.merigo@univr.it
Telephone: +39-45-8027155 Fax: +39-45-8027163
Received: December 6, 2017
Peer-review started: December 6, 2017
First decision: December 12, 2017
Revised: December 13, 2017
Accepted: December 19, 2017
Article in press: December 19, 2017
Published online: February 21, 2018
Processing time: 64 Days and 15.3 Hours
Abstract
AIM

To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease (IBD).

METHODS

Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or recto-sigmoidoscopy. Patients diagnosed with ulcerative colitis (n = 18) or Crohn’s disease (n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group (CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, double-labeled confocal microscopy was used.

RESULTS

Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive (-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and non-inflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels.

CONCLUSION

Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.

Keywords: Ulcerative colitis; Colon; Crohn’s disease; Glucose transporter; LYVE-1, Immunohistochemistry

Core tip: Our study demonstrates that GLUT2, SGLT1, and GLUT5 glucose transporters are expressed in the colorectal mucosa in controls and patients with inflammatory bowel disease (IBD). In addition, it provides first evidence that GLUT5 expression is associated with lymphatic vessels in controls and IBD patients. GLUT5-immunoreactive vessels were isolated or clustered in specific areas. We interpreted the presence of clusters as a pattern related to proliferative zones. As GLUT5 is the main fructose transporter, fructose may have a role in the atypical aggregation of lymphatic vessels. This novel finding yields further insight into the characterization of lymphatic vasculature, whose dysfunction is a long-recognized feature in humans with IBD.