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Targeted deletion of Atg5 in intestinal epithelial cells promotes dextran sodium sulfate-induced colitis.

NISHINO Kyohei NISHIDA Atsushi 90719915 0000-0002-1288-3272 INATOMI Osamu 70530351 0000-0002-5837-6575 IMAI Takayuki 0000-0002-9170-4075 KUME Shinji 00452235 0000-0001-6937-9715 KAWAHARA Masahiro 80617449 0000-0002-2721-7571 MAEGAWA Hiroshi 00209363 0000-0002-4611-8149 ANDOH Akira 90252395 0000-0001-8533-2669 滋賀医科大学

2021

概要

Autophagy-associated genes have been identified as susceptible loci for inflammatory bowel disease. We investigated the role of a core autophagy factor, Atg5, in the development of dextran sodium sulfate (DSS)-induced colitis. Intestinal epithelial cell (IEC)-specific Atg5 gene deficient mice (Atg5ΔIEC mice) were generated by cross of Atg5-floxed mice (Atg5fl/fl) with transgenic mice expressing Cre-recombinase driven by the villin promotor. Mice were given three cycles of 1.5% DSS in drinking water for 5 days and regular water for 14 days over a 60-day period. The dysfunction of autophagy characterized by a marked accumulation of p62 protein, a substrate for autophagy degradation, was detected in epithelial cells in the non-inflamed and inflamed mucosa of inflammatory bowel disease patients. DSS-colitis was exacerbated in Atg5ΔIEC mice compared to control Atg5fl/fl mice. Phosphorylation of inositol-requiring transmembrane kinase/endonuclease1α (IRE1α), a sensor for endoplasmic reticulum stress, and c-Jun N-terminal kinase, a downstream target of IRE1α, were significantly enhanced in IECs in DSS-treated Atg5ΔIEC mice. Accumulation of phosphorylated IRE1α was enhanced by the treatment with chloroquine, an autophagy inhibitor. Apoptotic IECs were more abundant in DSS-treated Atg5ΔIEC mice. These findings suggest that Atg5 suppresses endoplasmic reticulum stress-induced apoptosis of IECs via the degradation of excess p-IRE1α.

参考文献

1 Verstockt B, Ferrante M, Vermeire S, Van Assche G. New treatment options

for inflammatory bowel diseases. J Gastroenterol 2018; 53: 585–590.

2 Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev

Immunol 2010; 28: 573–621.

3 Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417–

429.

4 Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y. Autophagy in yeast

demonstrated with proteinase-deficient mutants and conditions for its

induction. J Cell Biol 1992; 119: 301–311.

5 Baxt LA, Xavier RJ. Role of autophagy in the maintenance of intestinal

homeostasis. Gastroenterology 2015; 149: 553–562.

6 Goldman SJ, Zhang Y, Jin S. Autophagic degradation of mitochondria in

white adipose tissue differentiation. Antioxid Redox Signal 2011; 14: 1971–

1978.

7 Mortensen M, Ferguson DJ, Edelmann M, et al. Loss of autophagy in

erythroid cells leads to defective removal of mitochondria and severe anemia

in vivo. Proc Natl Acad Sci U S A 2010; 107: 832–837.

8 Jiang P, Mizushima N. Autophagy and human diseases. Cell Res 2014; 24:

69–79.

9 Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study

identifies new susceptibility loci for Crohn disease and implicates autophagy

in disease pathogenesis. Nat Genet 2007; 39: 596–604.

10 Cadwell K. Crosstalk between autophagy and inflammatory signalling

pathways: balancing defence and homeostasis. Nat Rev Immunol 2016; 16:

661–675.

11 Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress: cell life and

death decisions. J Clin Invest 2005; 115: 2656–2664.

12 Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded

protein response. Nat Rev Mol Cell Biol 2007; 8: 519–529.

13 Rao RV, Bredesen DE. Misfolded proteins, endoplasmic reticulum stress and

neurodegeneration. Curr Opin Cell Biol 2004; 16: 653–662.

14 Kaser A, Lee AH, Franke A, et al. XBP1 links ER stress to intestinal

inflammation and confers genetic risk for human inflammatory bowel

disease. Cell 2008; 134: 743–756.

15 Cao SS. Epithelial ER stress in Crohn’s disease and ulcerative colitis.

Inflamm Bowel Dis 2016; 22: 984–993.

16 Hooper KM, Barlow PG, Henderson P, Stevens C. Interactions between

autophagy and the unfolded protein response: implications for inflammatory

bowel disease. Inflamm Bowel Dis 2019; 25: 661–671.

17 Sugiyama T, Sasaki M, Nakagawa S, et al. The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative

colitis. J Clin Biochem Nutr 2020; 66: 152–157.

18 Deuring JJ, Fuhler GM, Konstantinov SR, et al. Genomic ATG16L1 risk

allele-restricted Paneth cell ER stress in quiescent Crohn’s disease. Gut 2014;

63: 1081–1091.

19 Adolph TE, Tomczak MF, Niederreiter L, et al. Paneth cells as a site of

origin for intestinal inflammation. Nature 2013; 503: 272–276.

20 Tschurtschenthaler M, Adolph TE, Ashcroft JW, et al. Defective ATG16L1mediated removal of IRE1a drives Crohn’s disease-like ileitis. J Exp Med

2017; 214: 401–422.

21 Codogno P, Meijer AJ. Atg5: more than an autophagy factor. Nat Cell Biol

2006; 8: 1045–1047.

162

22 Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo

analysis of autophagy in response to nutrient starvation using transgenic mice

expressing a fluorescent autophagosome marker. Mol Biol Cell 2004; 15:

1101–1111.

23 Yang YR, Kim DH, Seo YK, et al. Elevated O-GlcNAcylation promotes

colonic inflammation and tumorigenesis by modulating NF-kB signaling.

Oncotarget 2015; 6: 12529–12542.

24 Berberat PO, YI AR, Yamashita K, et al. Heme oxygenase-1-generated

biliverdin ameliorates experimental murine colitis. Inflamm Bowel Dis 2005;

11: 350–359.

25 Obermeier F, Kojouharoff G, Hans W, Schölmerich J, Gross V, Falk W.

Interferon-gamma (IFN-g)- and tumour necrosis factor (TNF)-induced nitric

oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)induced colitis in mice. Clin Exp Immunol 1999; 116: 238–245.

26 Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor

for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 2014; 40: 128–139.

27 Nishida A, Hidaka K, Kanda T, et al. Increased expression of interleukin-36,

a member of the interleukin-1 cytokine family, in inflammatory bowel

disease. Inflamm Bowel Dis 2016; 22: 303–314.

28 Hino K, Saito A, Asada R, Kanemoto S, Imaizumi K. Increased susceptibility

to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress

transducer OASIS deficient mice. PLoS One 2014; 9: e88048.

29 Bjørkøy G, Lamark T, Brech A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtininduced cell death. J Cell Biol 2005; 171: 603–614.

30 Mauthe M, Orhon I, Rocchi C, et al. Chloroquine inhibits autophagic flux by

decreasing autophagosome-lysosome fusion. Autophagy 2018; 14: 1435–1455.

31 Urano F, Wang X, Bertolotti A, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science

2000; 287: 664–666.

32 Qiu W, Wu B, Wang X, et al. PUMA-mediated intestinal epithelial apoptosis

contributes to ulcerative colitis in humans and mice. J Clin Invest 2011; 121:

1722–1732.

33 Frey MR, Edelblum KL, Mullane MT, Liang D, Polk DB. The ErbB4 growth

factor receptor is required for colon epithelial cell survival in the presence of

TNF. Gastroenterology 2009; 136: 217–226.

34 Patel KK, Stappenbeck TS. Autophagy and intestinal homeostasis. Annu Rev

Physiol 2013; 75: 241–262.

35 Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and

immunity. Nat Rev Immunol 2013; 13: 722–737.

36 Kaser A, Blumberg RS. Autophagy, microbial sensing, endoplasmic

reticulum stress, and epithelial function in inflammatory bowel disease.

Gastroenterology 2011; 140: 1738–1747.

37 Cadwell K, Patel KK, Komatsu M, Virgin HW 4th, Stappenbeck TS. A

common role for Atg16L1, Atg5 and Atg7 in small intestinal Paneth cells

and Crohn disease. Autophagy 2009; 5: 250–252.

38 Komatsu M, Waguri S, Koike M, et al. Homeostatic levels of p62 control

cytoplasmic inclusion body formation in autophagy-deficient mice. Cell

2007; 131: 1149–1163.

39 Pott J, Kabat AM, Maloy KJ. Intestinal epithelial cell autophagy is required

to protect against TNF-induced apoptosis during chronic colitis in mice. Cell

doi: 10.3164/jcbn.2090

©2021 JCBN

Host Microbe 2018; 23: 191–202.e4.

40 Credle JJ, Finer-Moore JS, Papa FR, Stroud RM, Walter P. On the

mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc

Natl Acad Sci U S A 2005; 102: 18773–18784.

41 Sun S, Shi G, Sha H, et al. IRE1a is an endogenous substrate of endoplasmicreticulum-associated degradation. Nat Cell Biol 2015; 17: 1546–1555.

42 Ghosh R, Wang L, Wang ES, et al. Allosteric inhibition of the IRE1a RNase

preserves cell viability and function during endoplasmic reticulum stress. Cell

2014; 158: 534–548.

43 Korennykh A, Walter P. Structural basis of the unfolded protein response.

Annu Rev Cell Dev Biol 2012; 28: 251–277.

44 Wu L, Liu X, Wang L, et al. Exendin-4 protects HUVECs from tunicamycin-

K. Nishino et al.

induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway. Endocrine

2017; 55: 764–772.

45 Li Q, Verma IM. NF-kB regulation in the immune system. Nat Rev Immunol

2002; 2: 725–734.

46 Keestra-Gounder AM, Byndloss MX, Seyffert N, et al. NOD1 and NOD2

signalling links ER stress with inflammation. Nature 2016; 532: 394–397.

This is an open access article distributed under the terms of the

Creative Commons Attribution-NonCommercial-NoDerivatives

License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

J. Clin. Biochem. Nutr. | March 2021 | vol. 68 | no. 2 | 163

©2021 JCBN

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