ZNF354C Mediated by DNMT1 Ameliorates Lung Ischemia-Reperfusion Oxidative Stress Injury by Reducing TFPI Promoter Methylation to Upregulate TFPI

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Aug 2

PMID 35915612

Authors

Qi Shi

Nana Feng

Qingyun Ma

Shaohua Wang

Huijun Zhang

Dayu Huang

Jiayuan Sun

Meng Shi

Affiliations

Soon will be listed here.

Abstract

Background: Pulmonary ischemia reperfusion- (I/R-) induced dysfunction is a significant clinical problem after lung transplantation. In this study, we aim to explore the molecular mechanism of lung I/R injury (LIRI).

Methods: Bioinformatic analysis of gene involved in oxidative stress. A HUVEC oxygen glucose deprivation/reoxygenation (OGD/R) model and I/R mouse model were first established via I/R. The cellular proliferation, migration, reactive oxygen species (ROS), and parameters of lung injury were assessed via CCK-8, EdU staining, Transwell, cellular ROS kit, and H&E staining. We also confirmed related gene expressions and protein levels and the interaction between the tissue factor pathway inhibitor (TFPI) promotor and ZNF354C.

Results: Bioinformatic analysis results showed TFPI contributed to oxidative stress. OGD/R caused a reduction in cell viability and migration, hypermethylation of TFPI, increased ROS, and downregulation of ZNF354C, TFPI, and DNA methyltransferases (DNMTs) in HUVECs. Besides, ZNF354C could directly bind to the TFPI promoter, enhance proliferation and migration, and inhibit ROS in OGD/R-induced HUVECs by upregulating TFPI. More importantly, we discovered that 5-Aza could reduce TFPI methylation, upregulate TFPI, and enhance the binding of ZNF354C to the TFPI promoter in LIRI. Furthermore, DNMT1 silencing could induce proliferation and migration and prevent ROS in OGD/R-induced HUVECs by upregulating ZNF354C. Additionally, we verified that ZNF354C could alleviate LIRI by preventing DNA methylation .

Conclusions: ZNF354C overexpression induced proliferation and migration, as well as suppressed ROS in OGD/R-induced HUVECs, and alleviated LIRI in mice by inhibiting TFPI promoter methylation to upregulate TFPI. Therefore, ZNF354C and TFPI methylation might be promising molecular markers for LIRI therapy.

Citing Articles

Retracted: ZNF354C Mediated by DNMT1 Ameliorates Lung Ischemia-Reperfusion Oxidative Stress Injury by Reducing TFPI Promoter Methylation to Upregulate TFPI.

Longevity O Oxid Med Cell Longev. 2024; 2023:9785630.

PMID: 38189022 PMC: 10769664. DOI: 10.1155/2023/9785630.

Inhibition of DNA methylation attenuates lung ischemia-reperfusion injury after lung transplantation.

Liu M, Ju Y, Jia B, Sun X, Qiu L, Liu H J Int Med Res. 2023; 51(2):3000605231153587.

PMID: 36756846 PMC: 9912569. DOI: 10.1177/03000605231153587.

References

Ficz G . New insights into mechanisms that regulate DNA methylation patterning. J Exp Biol. 2015; 218(Pt 1):14-20. DOI: 10.1242/jeb.107961. View

Liu B, Lan M, Wei H, Zhang D, Liu J, Teng J . Downregulated microRNA‑133a induces HUVECs injury: Potential role of the (pro) renin receptor in angiotensin II‑dependent hypertension. Mol Med Rep. 2019; 20(3):2796-2804. PMC: 6691251. DOI: 10.3892/mmr.2019.10519. View

Li Y, Liu T . Zinc Finger Proteins in the Human Fungal Pathogen . Int J Mol Sci. 2020; 21(4). PMC: 7072944. DOI: 10.3390/ijms21041361. View

Vaitkiene P, Skiriute D, Skauminas K, Tamasauskas A . Associations between TFPI-2 methylation and poor prognosis in glioblastomas. Medicina (Kaunas). 2012; 48(7):345-9. View

Tang J, Zhuang S . Histone acetylation and DNA methylation in ischemia/reperfusion injury. Clin Sci (Lond). 2019; 133(4):597-609. PMC: 7470454. DOI: 10.1042/CS20180465. View

Geng G, Liu X, Xu A, Lu Z, Chen K, He J . Low abundance of TFPI-2 by both promoter methylation and miR-27a-3p regulation is linked with poor clinical outcome in gastric cancer. J Gene Med. 2020; 22(5):e3166. DOI: 10.1002/jgm.3166. View

Li Z, Lu X, Liu Y, Zhao J, Ma S, Yin H . Gain of LINC00624 Enhances Liver Cancer Progression by Disrupting the Histone Deacetylase 6/Tripartite Motif Containing 28/Zinc Finger Protein 354C Corepressor Complex. Hepatology. 2020; 73(5):1764-1782. DOI: 10.1002/hep.31530. View

Thomassen M, Heinzmann A, Herfs L, Hartmann R, Dockal M, Scheiflinger F . Tissue factor-independent inhibition of thrombin generation by tissue factor pathway inhibitor-α. J Thromb Haemost. 2014; 13(1):92-100. DOI: 10.1111/jth.12766. View

Chambers E, Rounds S, Lu Q . Pulmonary Endothelial Cell Apoptosis in Emphysema and Acute Lung Injury. Adv Anat Embryol Cell Biol. 2017; 228:63-86. PMC: 5930489. DOI: 10.1007/978-3-319-68483-3_4. View

10.

Wang Y, Wang X, Zhang H, Han B, Ye Y, Zhang M . Transforming Growth Factor-β1 Promotes M1 Alveolar Macrophage Polarization in Acute Lung Injury by Up-Regulating DNMT1 to Mediate the microRNA-124/PELI1/IRF5 Axis. Front Cell Infect Microbiol. 2021; 11:693981. PMC: 8421846. DOI: 10.3389/fcimb.2021.693981. View

11.

Talaie T, DiChiacchio L, Prasad N, Pasrija C, Julliard W, Kaczorowski D . Ischemia-reperfusion Injury in the Transplanted Lung: A Literature Review. Transplant Direct. 2021; 7(2):e652. PMC: 7793349. DOI: 10.1097/TXD.0000000000001104. View

12.

Zhang L, Lu Q, Chang C . Epigenetics in Health and Disease. Adv Exp Med Biol. 2020; 1253:3-55. DOI: 10.1007/978-981-15-3449-2_1. View

13.

Zhang Y, Xu Y, Li Z, Zhu Y, Wen S, Wang M . Identification of the key transcription factors in esophageal squamous cell carcinoma. J Thorac Dis. 2018; 10(1):148-161. PMC: 5863113. DOI: 10.21037/jtd.2017.12.27. View

14.

Fullar A, Karaszi K, Hollosi P, Lendvai G, Olah L, Reszegi A . Two ways of epigenetic silencing of TFPI2 in cervical cancer. PLoS One. 2020; 15(6):e0234873. PMC: 7304613. DOI: 10.1371/journal.pone.0234873. View

15.

Li J, Yang C, Wang Y . miR‑126 overexpression attenuates oxygen‑glucose deprivation/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/Nrf2 signaling pathway in human umbilical vein endothelial cells. Mol Med Rep. 2020; 23(2). PMC: 7789090. DOI: 10.3892/mmr.2020.11804. View

16.

Wood J, Ellery P, Maroney S, Mast A . Biology of tissue factor pathway inhibitor. Blood. 2014; 123(19):2934-43. PMC: 4014837. DOI: 10.1182/blood-2013-11-512764. View

17.

Svedruzic Z . Dnmt1 structure and function. Prog Mol Biol Transl Sci. 2011; 101:221-54. DOI: 10.1016/B978-0-12-387685-0.00006-8. View

18.

Sharma A, Charles E, Zhao Y, Narahari A, Baderdinni P, Good M . Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2018; 315(2):L301-L312. PMC: 6139659. DOI: 10.1152/ajplung.00004.2018. View

19.

Shao L, Fan J, Wang R, Feng L, Zhen C, Sui X . [Expression of TFPI-2 gene and its promoter methylation in acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014; 22(4):920-6. DOI: 10.7534/j.issn.1009-2137.2014.04.008. View

20.

Alsterda A, Asha K, Powrozek O, Repak M, Goswami S, Dunn A . Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway. Front Oncol. 2021; 11:654940. PMC: 8173155. DOI: 10.3389/fonc.2021.654940. View