DNA Methylation on Regulation of Cell Apoptosis and Proliferation in Ischemia-Reperfusion of Small Intestine_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 AN Shucai ^1,2 , WANG Qingfa ¹ , WANG Shuqing. ¹

1.The First Department of General Surgery， Affiliated Hospital of Medical College， Jiamusi University， Jiamusi 154002， Heilongjiang Province， China;;
2.Department of Thyroid Surgery， Affiliated Hospital of Medical College， Qingdao University， Qingdao 266003， Shandong Province， China;

Corresponding author：

AN Shucai, Email: ansc63@sohu.com

Keywords：

DNA methylation; Apoptosis; Proliferation; Ischemia-reperfusion; Small intestine

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the role of DNA methylation on regulation of cell apoptosis and proliferation in ischemia-reperfusion of small intestine.
Methods 　Thirty-five male Wistar rats were randomly divided into normal group， sham operation group， and ischemia-reperfusion group. The apoptotic cell was assessed by TUNEL and electron microscopy and the expression of Ki-67 was examined by immunohistochemistry in the small intestinal parts （villi epithe-lium， crypt epithelium， and lamina propria mucosa of small intestine）. The DNA methylation was detected by DNA histo-endonuclease-linked detection of methylated DNA sites. Results　①The apoptotic positive cells increased at 3 h， 6 h，and 12 h after ischemia-reperfusion in the villi epithelium， crypt epithelium， and lamina propria mucosa of small intestine as compared with the normal group and sham operation group （P＜0.01）；Moreover， the apoptotic cells in the lamina propria mucosa of small intestine were identified as T cells by electron microscopy. ②The expressions of Ki-67 markedly increased at 3 h， 6 h， 12 h， and 24 h after ischemia-reperfusion in the villi epithelium cells as compared with the normal group and sham operation group （P＜0.01）. ③The weak expression of DNA methylation was found in the villi epith-elium and crypt epithelium in the normal group and sham operation group， the b expression was examined in the crypt epithelium cells nearby stem cell site in the ischemia-reperfusion of small intestine， the change of expression was gradually weak from crypt epithelium to villi epithelium.
Conclusion 　This initial results indicate that the DNA methyl-ation in the ischemia-reperfusion of small intestine might regulate cell apoptosis and proliferation.

Citation： AN Shucai,WANG Qingfa,WANG Shuqing.. DNA Methylation on Regulation of Cell Apoptosis and Proliferation in Ischemia-Reperfusion of Small Intestine. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(11): 1234-1239. doi: Copy

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2.	An S， Hishikawa Y， Koji T. Induction of cell death in rat small intestine by ischemia reperfusion：differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types[J]. Histochem Cell Biol， 2005， 123(3)：249-261.
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24.	Eslaminejad MB， Fani N， Shahhoseini M. Epigenetic regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in culture[J]. Cell， 2013， 15(1)：1-10．.
25.	李望，钱国伟，徐为，等. DNA甲基化对Ki-67启动子转录活性的影响[J]. 中华实验外科杂志， 2011， 28(6)：901-903.

1. Hassoun HT， Zou L， Moore FA， et al. Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury[J]. Am J Physiol Gastrointest Liver Physiol， 2002， 282(6)：G1059-G1068.
2. An S， Hishikawa Y， Koji T. Induction of cell death in rat small intestine by ischemia reperfusion：differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types[J]. Histochem Cell Biol， 2005， 123(3)：249-261.
3. Jackson-Grusby L， Beard C， Possemato R， et al. Loss of genomicmethylation causes p53-dependent apoptosis and epigenetic deregulation[J]. Nat Genet， 2001， 27(1)：31-39.
4. Herman JG， Baylin SB. Gene silencing in cancer in association with promoter hypermethylation[J]. N Engl J Med， 2003， 349(21)：2042-2054.
5. Rao X， Zhong J， Zhang S， et al. Loss of methyl-CpG-binding domain protein 2 enhances endothelial angiogenesis and protects mice against hind-limb ischemic injury[J]. Circulation， 2011， 123(25)：2964-2974.
6. Westberry JM， Wilson ME. Regulation of estrogen receptor alpha gene expression in the mouse prefrontal cortex during early postnatal development[J]. Neurogenetics， 2012， 13(2)：159-167.
7. Skowronski K， Dubey S， Rodenhiser D， et al. Ischemia dysregul-ates DNA methyltransferases and p16INK4a methylation in humancolorectal cancer cells[J]. Epigenetics， 2010， 5(6)：547-556.
8. Hashimoto S， Koji T， Niu J， et al. Differential staining of DNA strand breaks in dying cells by non-radioactive in situ nick transla-tion[J]. Arch Histol Cytol， 1995， 58(2)：161-170.
9. An S， Hishikawa Y， Liu J， et al．Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type Ⅱ alveolar epithelial cells mediated by TNF-alpha and activation of Bid pathway[J]. Apoptosis， 2007， 12(11)：1989-2001.
10. Koji T， Kondo S， Hishikawa Y， et al. In situ detection of methylated DNA by histo endonuclease-linked detection of methylated DNA sites：a new principle of analysis of DNA methylation[J]. Histochem Cell Biol， 2008， 130(5)：917-925.
11. Otterson MF， Nie L， Schmidt JL， et al. EUK-207 protects humanintestinal microvascular endothelial cells (HIMEC) against irradi-ation-induced apoptosis through the Bcl2 pathway[J]. Life Sci， 2012， 91(15-16)：771-782.
12. Reardon C， Wang A， McKay DM. Transient local depletion of Foxp3+ regulatory T cells during recovery from colitis via Fas/Fas ligand-induced death[J]. J Immunol， 2008， 180(12)：8316-8326.
13. Neal MD， Sodhi CP， Jia H， et al. Toll-like receptor 4 is expressedon intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis[J]. J Biol Chem， 2012， 287(44)：37296-37308.
14. Riehl TE， Foster L， Stenson WF. Hyaluronic acid is radioprote-ctive in the intestine through a TLR4 and COX-2-mediated mech-anism[J]. Am J Physiol Gastrointest Liver Physiol， 2012， 302(3)：G309-G316.
15. Booth C， Potten CS. Gut instincts：thoughts on intestinal epithelialstem cells[J]. J Clin Invest， 2000， 105(11)：1493-1499.
16. Dekaney CM， Fong JJ， Rigby RJ， et al. Expansion of intestinalstem cells associated with long-term adaptation following ileocecalresection in mice[J]. Am J Physiol Gastrointest Liver Physiol， 2007， 293(5)：1013-1022.
17. Shibata D. Mistakes make history：visualizing intestinal tectonics[J]. Gastroenterology， 2008， 134(2)：628-631.
18. McDonald SA， Greaves LC， Gutierrez-Gonzalez L， et al. Mech-anisms of field cancerization in the human stomach：the expansionand spread of mutated gastric stem cells[J]. Gastroenterology， 2008， 134(2)：500-510.
19. Barros SP， Offenbacher S. Epigenetics：connecting environment and genotype to phenotype and disease[J]. J Dent Res， 2009， 88(5)：400-408.
20. Dumitrescu RG. DNA methylation and histone modifications in breast cancer[J]. Methods Mol Biol， 2012， 863：35-45. doi：10.1007/978-1-61779-612-8_3.
21. Maegawa S， Hinkal G， Kim HS， et al. Widespread and tissuespecific age-related DNA methylation changes in mice[J]. Gen-ome Res， 2010， 20(3)：332-340.
22. Kocemba K， Groen R， van Andel H， et al. Transcriptional silen-cing of the Wnt-Antagonist DKK1 by promoter methylation isassociated with enhanced Wnt signaling in advanced multiple mye-loma[J]. PLoS One， 2012， 7：e30359.
23. Hur K， Niwa T， Toyoda T， et al. Insufficient role of cell proliferation in aberrant DNA methylation induction and involvement of specific types of inflammation[J]. Carcinogenesis， 2011， 32(1)：35-41.
24. Eslaminejad MB， Fani N， Shahhoseini M. Epigenetic regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in culture[J]. Cell， 2013， 15(1)：1-10．.
25. 李望，钱国伟，徐为，等. DNA甲基化对Ki-67启动子转录活性的影响[J]. 中华实验外科杂志， 2011， 28(6)：901-903.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

DNA Methylation on Regulation of Cell Apoptosis and Proliferation in Ischemia-Reperfusion of Small Intestine

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