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International Journal of Colorectal Disease

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01-09-2015 | Original Article

Surgical diverticulitis is not associated with defects in the expression of wound healing genes

Authors: Tara M. Connelly, Arthur S. Berg, Leonard R. Harris III, Rafel Tappouni, Dave Brinton, Sue Deiling, Walter A. Koltun

Published in: International Journal of Colorectal Disease | Issue 9/2015

Abstract

Purpose

The development of diverticuli may represent defects in collagen vascular tissue integrity possibly from a genetic predisposition. We evaluated the tissue expression of wound healing genes in sigmoid tissue from youthful patients undergoing surgery for diverticulitis and thus would more likely suffer from a genetic predisposition (SD mean age 39 ± 0.9) versus controls in the form of patients over the age of 50 (mean age 52.9 ± 10.5 years) without evidence of diverticular disease.

Methods

The mRNA expression of 84 genes associated with the extracellular matrix, cellular adhesion, growth factors, inflammatory cytokines, and signal transduction was evaluated in 16 SD and 15 control tissues using a Qiagen^™ Wound Healing Array. Vitronectin, the gene protein with the highest potential significance on raw analysis, was further investigated using a Taqman assay with an additional 11 SD (total n = 27) and four control (total n = 19) samples. Statistics were by Student’s t and Mann-Whitney tests with Bonferroni correction.

Results

No significant differences in mRNA expression between the SD and control tissue in the 84 measured genes were demonstrated after correction. Vitronectin mRNA expression was downregulated 2.7-fold in SD tissue vs. tissue from non-neoplastic control patients (p = 0.001 raw/0.08 corrected). However, on vitronectin TaqMan analysis, no difference in expression was seen in SD vs. all controls or in all subset comparisons.

Conclusions

The lack of significant alteration in mRNA expression of traditionally associated wound healing genes/proteins in young SD patients suggests that such genes play a minor role in the genetic predisposition to youthful diverticulitis.

Strate LL, Liu YL, Aldoori WH, Syngal S, Giovannucci EL (2009) Obesity increases the risks of diverticulitis and diverticular bleeding. Gastroenterology 136:115–122. doi:10.1053/j.gastro.2008.09.025 PubMedCentralCrossRefPubMed

Zaidi E, Daly B (2006) CT and clinical features of acute diverticulitis in an urban U.S. population: rising frequency in young, obese adults. AJR Am J Roentgenol 187:689–694CrossRefPubMed

Rosemar A, Angeras U, Rosengren A (2008) Body mass index and diverticular disease: a 28-year follow-up study in men. Dis Colon Rectum 51:450–455CrossRefPubMed

Manousos O, Day NE, Tzonou A, Papadimitriou C, Kapetanakis A, Polychronopoulou-Trichopoulou A, Trichopoulos D (1985) Diet and other factors in the aetiology of diverticulosis: an epidemiological study in Greece. Gut 26:544–549PubMedCentralCrossRefPubMed

Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Trichopoulos DV, Willett WC (1994) A prospective study of diet and the risk of symptomatic diverticular disease in men. Am J Clin Nutr 60:757–764PubMed

Aldoori WH, Giovannucci EL, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Wing AL, Trichopoulos DV, Willett WC (1995) Prospective study of physical activity and the risk of symptomatic diverticular disease in men. Gut 36:276–282PubMedCentralCrossRefPubMed

Crowe FL, Appleby PN, Allen NE, Key TJ (2011) Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians. BMJ 343:d4131. doi:10.1136/bmj.d4131 PubMedCentralCrossRefPubMed

Ulmer TF, Rosch R, Mossdorf A, Alizai H, Binnebosel M, Neumann U (2014) Colonic wall changes in patients with diverticular disease—is there a predisposition for a complicated course? Int J Surg. doi:10.1016/j.ijsu.2014.03.014 PubMed

Altadill A, Eiro N, Gonzalez LO, Junquera S, González-Quintana JM, Sánchez MR, Andicoechea A, Saro C, Rodrigo L, Vizoso FJ (2012) Comparative analysis of the expression of metalloproteases and their inhibitors in resected Crohn’s disease and complicated diverticular disease. Inflamm Bowel Dis 18:120–130. doi:10.1002/ibd.21682 CrossRefPubMed

10.

Wess L, Eastwood MA, Wess TJ, Busuttil A, Miller A (1995) Cross linking of collagen is increased in colonic diverticulosis. Gut 37:91–94PubMedCentralCrossRefPubMed

11.

Stumpf M, Krones CJ, Klinge U, Rosch R, Junge K, Schumpelick V (2006) Collagen in colon disease. Hernia 10:498–501CrossRefPubMed

12.

Mimura T, Bateman AC, Lee RL, Johnson PA, McDonald PJ, Talbot IC, Kamm MA, MacDonald TT, Pender SL (2004) Up-regulation of collagen and tissue inhibitors of matrix metalloproteinase in colonic diverticular disease. Dis Colon Rectum 47:371–378, discussion 378-379 CrossRefPubMed

13.

Stumpf M, Cao W, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick V (2001) Increased distribution of collagen type III and reduced expression of matrix metalloproteinase 1 in patients with diverticular disease. Int J Color Dis 16:271–275CrossRef

14.

Pogacnik J, Messaris E, Deiling SM, Connelly TM, Berg AS, Stewart DB, McKenna KJ, Poritz LS, Koltun WA (2014) Increased risk of incisional hernia after sigmoid colectomy for diverticulitis compared with colon cancer. J Am Coll Surg 218:920–928. doi:10.1016/j.jamcollsurg.2014.01.050 CrossRefPubMed

15.

Claassen AT, Mourad-Baars PE, Mearin ML, Hilhorst-Hofstee Y, Gerritsen van der Hoop A (2006) Two siblings below the age of 20 years with diverticular disease. Int J Color Dis 21:190–191CrossRef

16.

Schlotthauer HL (1946) Familial diverticulosis of the colon: report of seven cases in one family of nine persons. Ann Surg 124:497–502PubMedCentralCrossRef

17.

Omojola MF, Mangete E (1988) Diverticula of the colon in three Nigerian siblings. Trop Geogr Med 40:54–57PubMed

18.

Santin BJ, Prasad V, Caniano DA (2009) Colonic diverticulitis in adolescents: an index case and associated syndromes. Pediatr Surg Int 25:901–905. doi:10.1007/s00383-009-2472-1 CrossRefPubMed

19.

Granlund J, Svensson T, Olen O, Hjern F, Pedersen NL, Magnusson PK, Schmidt PT (2012) The genetic influence on diverticular disease—a twin study. Aliment Pharmacol Ther. doi:10.1111/j.1365-2036.2012.05069.x

20.

Manwaring M (2011) Diverticular disease: genetic, geographic and environmental aspects. Semin Colon Rectal Surg 22:148–153CrossRef

21.

Scheff RT, Zuckerman G, Harter H, Delmez J, Koehler R (1980) Diverticular disease in patients with chronic renal failure due to polycystic kidney disease. Ann Intern Med 92:202–204CrossRefPubMed

22.

Connelly TM, Berg AS, Hegarty JP, Deiling S, Brinton D, Poritz LS, Koltun WA (2014) The TNFSF15 gene single nucleotide polymorphism Rs7848647 is associated with surgical diverticulitis. Ann Surg 259:1132–1137. doi:10.1097/SLA.0000000000000232 CrossRefPubMed

23.

Qiagen. Human Wound Healing Array (2014) http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-121Z.html. Accessed April 24, 2014

24.

Melendez-Zajgla J, Del Pozo L, Ceballos G, Maldonado V (2008) Tissue inhibitor of metalloproteinases-4. The road less traveled. Mol Cancer 7:85. doi:10.1186/1476-4598-7-85 PubMedCentralCrossRefPubMed

25.

Preissner KT, Seiffert D (1998) Role of vitronectin and its receptors in haemostasis and vascular remodeling. Thromb Res 89:1–21CrossRefPubMed

26.

Singh B, Su YC, Riesbeck K (2010) Vitronectin in bacterial pathogenesis: a host protein used in complement escape and cellular invasion. Mol Microbiol 78:545–560. doi:10.1111/j.1365-2958.2010.07373.x CrossRefPubMed

27.

Lakatos G, Sipos F, Miheller P, Hritz I, Varga MZ, Juhász M, Molnár B, Tulassay Z, Herszényi L (2012) The behavior of matrix metalloproteinase-9 in lymphocytic colitis, collagenous colitis and ulcerative colitis. Pathol Oncol Res 18:85–91. doi:10.1007/s12253-011-9420-9 CrossRefPubMed

28.

von Rahden BH, Jurowich C, Kircher S, Lazariotou M, Jung M, Germer CT, Grimm M (2012) Allergic predisposition, histamine and histamine receptor expression (H1R, H2R) are associated with complicated courses of sigmoid diverticulitis. J Gastrointest Surg 16:173–182. doi:10.1007/s11605-011-1702-8, discussion 182 CrossRef

29.

Costedio MM, Coates MD, Danielson AB, Buttolph TR 3rd, Blaszyk HJ, Mawe GM, Hyman NH (2008) Serotonin signaling in diverticular disease. J Gastrointest Surg 12:1439–1445. doi:10.1007/s11605-008-0536-5 PubMedCentralCrossRefPubMed

30.

de Vries HS, Plantinga TS, van Krieken JH, Stienstra R, van Bodegraven AA, Festen EA, Weersma RK, Crusius JB, Linskens RK, Joosten LA, Netea MG, de Jong DJ (2009) Genetic association analysis of the functional c.714T>G polymorphism and mucosal expression of dectin-1 in inflammatory bowel disease. PLoS One 4, e7818. doi:10.1371/journal.pone.0007818 PubMedCentralCrossRefPubMed

Title: Surgical diverticulitis is not associated with defects in the expression of wound healing genes
Authors: Tara M. Connelly
Arthur S. Berg
Leonard R. Harris III
Rafel Tappouni
Dave Brinton
Sue Deiling
Walter A. Koltun
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 9/2015
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-015-2263-1

At a glance: The STEP trials

Springer Medicine

Surgical diverticulitis is not associated with defects in the expression of wound healing genes

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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