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AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease

  • Authors:
    • Tian‑Jing Liu
    • Yong‑Yan Shi
    • En‑Bo Wang
    • Tong Zhu
    • Qun Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1156-1162
    |
    Published online on: December 14, 2015
       https://doi.org/10.3892/mmr.2015.4686
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Abstract

Angiotensin Ⅱ, which is the main effector of the renin‑angiotensin system, has an important role in intestinal inflammation via the angiotensin Ⅱ type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6‑trinitrobenzenesulphonic acid (TNBS)‑induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription‑quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis‑related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS‑induced body weight loss and colonic damage. Furthermore, T helper 1‑mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan‑treated mice. Losartan also increased the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) ratio and suppressed caspase‑3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS‑induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl‑2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase‑3.
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1 

Abraham C and Cho JH: Inflammatory bowel disease. N Engl J Med. 361:2066–2078. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Podolsky DK: Inflammatory bowel disease. N Engl J Med. 347:417–429. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Peterson LW and Artis D: Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat Rev Immunol. 14:141–153. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Jaszewski R, Tolia V, Ehrinpreis MN, Bodzin JH, Peleman RR, Korlipara R and Weinstock JV: Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis. Gastroenterology. 98:1543–1548. 1990.PubMed/NCBI

5 

Garg M, Burrell LM, Velkoska E, Griggs K, Angus PW, Gibson PR and Lubel JS: Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study. J Renin Angiotensin Aldosterone Syst. 16:559–569. 2015. View Article : Google Scholar

6 

Bregonzio C, Armando I, Ando H, Jezova M, Baiardi G and Saavedra JM: Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury. Am J Physiol Gastrointest Liver Physiol. 285:G414–G423. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Kuno A, Yamada T, Masuda K, Ogawa K, Sogawa M, Nakamura S, Nakazawa T, Ohara H, Nomura T, Joh T, et al: Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats. Gastroenterology. 124:1010–1019. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Inokuchi Y, Morohashi T, Kawana I, Nagashima Y, Kihara M and Umemura S: Amelioration of 2,4,6-trinitrobenzene sulphonic acid induced colitis in angiotensinogen gene knockout mice. Gut. 54:349–356. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Katada K, Yoshida N, Suzuki T, Okuda T, Mizushima K, Takagi T, Ichikawa H, Naito Y, Cepinskas G and Yoshikawa T: Dextran sulfate sodium-induced acute colonic inflammation in angiotensin II type 1a receptor deficient mice. Inflamm Res. 57:84–91. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J and Anversa P: Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest. 101:1326–1342. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Wang W, Sun L, Xiao W and Yang H: Essential role of angiotensin receptors in the modulation of intestinal epithelial cell apoptosis. J Pediatr Gastroenterol Nutr. 57:562–569. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Pawlowski J and Kraft AS: Bax-induced apoptotic cell death. Proc Natl Acad Sci USA. 97:529–531. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Tang Y, Swartz-Basile DA, Swietlicki EA, Yi L, Rubin DC and Levin MS: Bax is required for resection-induced changes in apoptosis, proliferation, and members of the extrinsic cell death pathways. Gastroenterology. 126:220–230. 2004. View Article : Google Scholar

14 

Czabotar PE, Lessene G, Strasser A and Adams JM: Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat Rev Mol Cell Biol. 15:49–63. 2014. View Article : Google Scholar

15 

Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR and Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 96:795–803. 1989.PubMed/NCBI

16 

Wengrower D, Zanninelli G, Latella G, Necozione S, Metanes I, Israeli E, Lysy J, Pines M, Papo O and Goldin E: Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats. Can J Gastroenterol. 26:33–39. 2012.PubMed/NCBI

17 

Appleyard CB and Wallace JL: Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol. 269:G119–G125. 1995.PubMed/NCBI

18 

Liu W, Chen Y, Golan MA, Annunziata ML, Du J, Dougherty U, Kong J, Musch M, Huang Y, Pekow J, et al: Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis. J Clin Invest. 123:3983–3996. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Su L, Nalle SC, Shen L, Turner ES, Singh G, Breskin LA, Khramtsova EA, Khramtsova G, Tsai PY, Fu YX, et al: TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology. 145:407–415. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Brand S: Crohn's disease: Th1, Th17 or both? The change of a paradigm: New immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut. 58:1152–1167. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Hume GE and Radford-Smith GL: ACE inhibitors and angiotensin II receptor antagonists in Crohn's disease management. Expert Rev Gastroenterol Hepatol. 2:645–651. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Spencer AU, Yang H, Haxhija EQ, Wildhaber BE, Greenson JK and Teitelbaum DH: Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition. Dig Dis Sci. 52:1060–1070. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Okawada M, Koga H, Larsen SD, Showalter HD, Turbiak AJ, Jin X, Lucas PC, Lipka E, Hillfinger J, Kim JS and Teitelbaum DH: Use of enterally delivered angiotensin II type 1a receptor antagonists to reduce the severity of colitis. Dig Dis Sci. 56:2553–2565. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Li X, Rayford H and Uhal BD: Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Am J Pathol. 163:2523–2530. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Hirasawa K, Sato Y, Hosoda Y, Yamamoto T and Hanai H: Immunohistochemical localization of angiotensin II receptor and local renin-angiotensin system in human colonic mucosa. J Histochem Cytochem. 50:275–282. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Petnehazy T, Cooper D, Stokes KY, Russell J, Wood KC and Granger DN: Angiotensin II type 1 receptors and the intestinal microvascular dysfunction induced by ischemia and reperfusion. Am J Physiol Gastrointest Liver Physiol. 290:G1203–G1210. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Mori M, Stokes KY, Vowinkel T, Watanabe N, Elrod JW, Harris NR, Lefer DJ, Hibi T and Granger DN: Colonic blood flow responses in experimental colitis: Time course and underlying mechanisms. Am J Physiol Gastrointest Liver Physiol. 289:G1024–G1029. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Deniz M, Cetinel S and Kurtel H: Blood flow alterations in TNBS-induced colitis: Role of endothelin receptors. Inflamm Res. 53:329–336. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Garrelds IM, Heiligers JP, Van Meeteren ME, Duncker DJ, Saxena PR, Meijssen MA and Zijlstra FJ: Intestinal blood flow in murine colitis induced with dextran sulfate sodium. Dig Dis Sci. 47:2231–2236. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu TJ, Shi YY, Wang EB, Zhu T and Zhao Q: AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease. Mol Med Rep 13: 1156-1162, 2016.
APA
Liu, T., Shi, Y., Wang, E., Zhu, T., & Zhao, Q. (2016). AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease. Molecular Medicine Reports, 13, 1156-1162. https://doi.org/10.3892/mmr.2015.4686
MLA
Liu, T., Shi, Y., Wang, E., Zhu, T., Zhao, Q."AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease". Molecular Medicine Reports 13.2 (2016): 1156-1162.
Chicago
Liu, T., Shi, Y., Wang, E., Zhu, T., Zhao, Q."AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease". Molecular Medicine Reports 13, no. 2 (2016): 1156-1162. https://doi.org/10.3892/mmr.2015.4686
Copy and paste a formatted citation
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Spandidos Publications style
Liu TJ, Shi YY, Wang EB, Zhu T and Zhao Q: AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease. Mol Med Rep 13: 1156-1162, 2016.
APA
Liu, T., Shi, Y., Wang, E., Zhu, T., & Zhao, Q. (2016). AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease. Molecular Medicine Reports, 13, 1156-1162. https://doi.org/10.3892/mmr.2015.4686
MLA
Liu, T., Shi, Y., Wang, E., Zhu, T., Zhao, Q."AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease". Molecular Medicine Reports 13.2 (2016): 1156-1162.
Chicago
Liu, T., Shi, Y., Wang, E., Zhu, T., Zhao, Q."AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease". Molecular Medicine Reports 13, no. 2 (2016): 1156-1162. https://doi.org/10.3892/mmr.2015.4686
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