Increased FoxO1 DNA methylation level in homocysteine-induced podocyte apoptosis

doi:10.3969/j.issn.2095-4344.2980

Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (2): 269-273.doi: 10.3969/j.issn.2095-4344.2980

Previous Articles Next Articles

Increased FoxO1 DNA methylation level in homocysteine-induced podocyte apoptosis

Liu Kun1, 2, 3, Xie Lin2, 3, 4, Cao Jun1, 2, 3, Ding Ning2, 3, 4, Xu Lingbo2, 3, 4, Ma Shengchao2, 3, 4, Li Guizhong2, 3, 4 , Jiang Yideng2, 3, 4, Lu Guanjun2, 3, 5

1Clinical Medical College, 4Basic Medical College, 3Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 2Key Laboratory of Metabolic Cardiovascular Disease Research of National Health Commission, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 5General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China

Received:2019-12-23 Revised:2019-12-28 Accepted:2020-02-26 Online:2021-01-18 Published:2020-11-21
Contact: Lu Guanjun, Master, Chief physician, Key Laboratory of Metabolic Cardiovascular Disease Research of National Health Commission, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China; General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
About author:Liu Kun, Master candidate, Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Metabolic Cardiovascular Disease Research of National Health Commission, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Ningxia Key Laboratory of Vascular Injury and Repair Research, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Supported by:
the National Natural Science Foundation of China, No. 81560120

Abstract

Abstract: BACKGROUND: The increase of homocysteine can lead to renal injury and podocyte apoptosis, but the specific mechanism is not clear.
OBJECTIVE: To investigate the effect of Forkhead box O1 (FoxO1) and its DNA methylation in podocyte apoptosis induced by homocysteine.
METHODS: Mouse renal podocytes (MPC-5) were cultured in vitro and divided into control group (0 μmol/L homocysteine) and homocysteine group (80 μmol/L homocysteine). After 48 hours of intervention, the expression of podocyte apoptosis-related proteins Bax, caspase12 and Bcl-2 was detected by immunofluorescence technique; the expression level of FoxO1 mRNA was detected by real-time fluorescence quantitative PCR; the protein expression levels of FoxO1 and DNMT1 were detected by western blot; DNA methylation level of FoxO1 was detected by nested methylation-specific PCR.
RESULTS AND CONCLUSION: Compared with the control group, the expression levels of Bax and caspase12 protein in podocytes of the homocysteine group were significantly increased, while the expression of Bcl-2 protein was significantly decreased. The expression levels of FoxO1 mRNA and protein were significantly decreased in the homocysteine group compared with the control group (P < 0.01). At the same time, the methylation level of FoxO1 DNA in the homocysteine group was significantly higher than that in the control group (P < 0.01), and the expression of DNMT1 protein in podocytes in the homocysteine group was significantly higher than that in the control group (P < 0.01). To conclude, FoxO1 DNA hypermethylation plays a significant role in podocyte apoptosis induced by homocysteine, whereas DNMT1 participates in homocysteine-induced podocyte apoptosis.

Key words: kidney, glomerulus, renal injury, homocysteine, podocyte, apoptosis, factor, methylation

CLC Number:

Liu Kun, Xie Lin, Cao Jun, Ding Ning, Xu Lingbo, Ma Shengchao, Li Guizhong , Jiang Yideng, Lu Guanjun. Increased FoxO1 DNA methylation level in homocysteine-induced podocyte apoptosis[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(2): 269-273.

Figures/Tables 4

References

[1] OSTRAKHOVITCH EA, TABIBZADEH S. Homocysteine in Chronic Kidney Disease. Adv Clin Chem. 2015;72:77-106.
[2] KARMIN O, SIOW YL. Metabolic Imbalance of Homocysteine and Hydrogen Sulfide in Kidney Disease. Curr Med Chem. 2018;25(3): 367-377.
[3] 叶增纯,黎燕,张俊,等.原发性肾小球肾炎患者高同型半胱氨酸血症的发生率及与靶器官损害之间的关系[J].中山大学学报(医学科学版),2016,37(6):869-874+880.
[4] CHEN X, ZHAO L, XING Y, et al. Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression. Biomed Pharmacother. 2018; 108:7-14.
[5] 蒲道静,郑府,徐先顺,等.萝卜硫素干预纳米细菌诱导肾小管上皮细胞凋亡及线粒体自噬相关蛋白的表达[J].中国组织工程研究,2019,23(34):5503-5507.
[6] WEI X, YANG X, WANG B, et al. LncRNA MBNL1-AS1 represses cell proliferation and enhances cell apoptosis via targeting miR-135a-5p/PHLPP2/FoxO1 axis in bladder cancer. Cancer Med. 2019 Nov 25.
[7] XING YQ, LI A, YANG Y, et al. The regulation of FoxO1 and it is role in disease progression. Life Sci. 2018;193:124-131.
[8] 谢琳,丁宁,徐灵博,等.FoxO1 DNA甲基化在同型半胱氨酸致肝细胞凋亡中的作用[J].实用医学杂志,2018,34(16):2659-2662+2669.
[9] HISHIKAWA A, HAYASHI K, ABE T, et al. Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes. Cell Rep. 2019;26(5):1318-1332.e4.
[10] LASSEIGNE BN,BROOKS JD.The Role of DNA Methylation in Renal Cell Carcinoma. Mol Diagn Ther. 2018;22(4):431-442.
[11] 丁宁,郭凤英,谢琳,等.miR-30a在同型半胱氨酸致足细胞凋亡中的作用[J].广东医学,2019,40(6):762-766.
[12] 李金红,陶建瓴,李航.足细胞损伤与糖尿病肾病的研究现状[J].中国医学科学院学报,2010,32(5):590-596.
[13] WU CC, ZHENG CM, LIN YF, et al. Role of homocysteine in end-stage renal disease. Clin Biochem. 2012; 45(16-17):1286-94.
[14] ZHOU YF, GUAN YF. [Hyperhomocysteinemia and kidney diseases]. Sheng Li Xue Bao. 2018;70(6):607-611.
[15] CIANCIOLO G,DE PASCALIS A,DI LULLO L,et al. Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First? Cardiorenal Med. 2017;7(4):255-266.
[16] FAN Y, ZHANG J, XIAO W, et al. Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy. Sci Rep. 2017;7(1): 323.
[17] WANG Y, LI H, SONG SP. β-Arrestin 1/2 Aggravates Podocyte Apoptosis of Diabetic Nephropathy via Wnt/β-Catenin Pathway. Med Sci Monit. 2018;24:1724-1732.
[18] WANG L, SCOTT I, ZHU L, et al. GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis. Nat Commun. 2017;8(1):523.
[19] 贺东黎.姜黄素通过ATK/FoxM1信号通路调控胃癌干细胞增殖及凋亡[J].中国组织工程研究,2016,20(32):4731-4737.
[20] CHAE YC, KIM JY, PARK JW, et al. FoxO1 degradation via G9a-mediated methylation promotes cell proliferation in colon cancer. Nucleic Acids Res. 2019;47(4):1692-1705.
[21] 张扬,吴朝蒙,雷博涵,等.PI3K/AKT/FoxO1信号通路参与复方中药CFF-1诱导的前列腺癌细胞凋亡和周期阻滞[J].中华男科学杂志,2017,23(09):828-837
[22] LIU Z, REN YA, PANGAS SA, et al. FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development. Mol Endocrinol. 2015; 29(7):1006-1024.
[23] TIRADO-MAGALLANES R, REBBANI K, LIM R, et al. Whole genome DNA methylation: beyond genes silencing. Oncotarget. 2017;8(3): 5629-5637.
[24] ZHANG L,ZHANG Q,LIU S,et al.DNA methyltransferases 1 may be a therapy target for attenuating diabetic nephropathy and podocyte injury. Kidney Int. 2017;92(1):140-153.
[25] 尹树慧,闫少春,周立社,等.肾细胞癌患者组织中RASSF1A、hMLH1及ALU甲基化水平的分析[J].临床检验杂志,2016,34(1): 31-34.
[26] 吴元,张文涛,马文超,等.SOX7启动子甲基化对膀胱癌增殖及凋亡的影响[J].医学研究生学报,2019,32(12):1285-1290.
[27] KIM M, COSTELLO J. DNA methylation: an epigenetic mark of cellular memory. Exp Mol Med. 2017 Apr 28;49(4):e322.
[28] MOORE LD, LE T, FAN G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23-38.
[29] AL-JAMAL HA,MAT JUSOH SA,HASSAN R,et al.Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia. BMC Cancer. 2015;15:869.
[30] 田平平,刘忠强,孔静,等.DNA甲基转移酶及分泌型卷曲相关蛋白1在糖尿病肾脏疾病大鼠肾组织中的表达研究[J].中国糖尿病杂志,2018,26(7):594-598.

Increased FoxO1 DNA methylation level in homocysteine-induced podocyte apoptosis

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Wu Liang, Wang Qiang, Wang Wenbo, Xin Tianwen, Xi Kun, Tang Jincheng, Xu Jingzhi, Chen Liang, Gu Yong. Risk factors for traumatic central cord syndrome underlying with cervical spondylotic myelopathy [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(9): 1388-1394.
[2]	Kong Yamin, Yan Juntao, Ma Bingxiang, Li Huawei. Massage vibration intervenes with MyoD expression and proliferation and differentiation of muscle satellite cells in rats with sciatic nerve injury [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1160-1166.
[3]	Wu Cong, Jia Quanzhong, Liu Lun. Relationship between transforming growth factor beta1 expression and chondrocyte migration in adult articular cartilage after fragmentation [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1167-1172.
[4]	Wang Baojuan, Zheng Shuguang, Zhang Qi, Li Tianyang. Miao medicine fumigation can delay extracellular matrix destruction in a rabbit model of knee osteoarthritis [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1180-1186.
[5]	Wang Qin, Shen Cheng, Liao Jing, Yang Ye. Dapagliflozin improves renal injury in diabetic nephropathy rats [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1216-1222.
[6]	Xiao Yang, Gong Liqiong, Fei Jing, Li Leiji. Effect of electroacupuncture on nerve growth factor and its receptor expression in facial nerve nucleus after facial nerve injury in rabbits [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1253-1259.
[7]	Tang Wenjing, Wu Siyuan, Yang Chen, Tao Xi. Inflammatory responses in post-stroke depression [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1278-1285.
[8]	An Weizheng, He Xiao, Ren Shuai, Liu Jianyu. Potential of muscle-derived stem cells in peripheral nerve regeneration [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1130-1136.
[9]	Liu Feng, Peng Yuhuan, Luo Liangping, Wu Benqing. Plant-derived basic fibroblast growth factor maintains the growth and differentiation of human embryonic stem cells [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1032-1037.
[10]	Wen Dandan, Li Qiang, Shen Caiqi, Ji Zhe, Jin Peisheng. Nocardia rubra cell wall skeleton for extemal use improves the viability of adipogenic mesenchymal stem cells and promotes diabetes wound repair [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1038-1044.
[11]	Luo Xiaoling, Zhang Li, Yang Maohua, Xu Jie, Xu Xiaomei. Effect of naringenin on osteogenic differentiation of human periodontal ligament stem cells [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1051-1056.
[12]	Zhang Yujie, Yang Jiandong, Cai Jun, Zhu Shoulei, Tian Yuan. Mechanism by which allicin inhibits proliferation and promotes apoptosis of rat vascular endothelial cells [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(7): 1080-1084.
[13]	He Shiping, Jia Dazhou, Li Xiaolei, Wang Qiang. Establishment of prediction model of blood transfusion after proximal femoral nail anti-rotation fixation of femoral intertrochanteric fracture in elderly adults [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 929-933.
[14]	Peng Kun. Improvement of the treatment effect of osteoporotic fractures: research status and strategy analysis [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 980-984.
[15]	Liu Jin, Li Zhen, Hao Huiqin, Wang Ze, Zhao Caihong, Lu Wenjing. Ermiao san aqueous extract regulates proliferation, migration, and inflammatory factor expression of fibroblast-like synovial cells in collagen-induced arthritis rats [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(5): 688-693.