PMID- 35114215 OWN - NLM STAT- MEDLINE DCOM- 20220421 LR - 20220531 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 217 DP - 2022 Apr TI - Runx1 regulates Tff1 expression to expedite viability of retinal microvascular endothelial cells in mice with diabetic retinopathy. PG - 108969 LID - S0014-4835(22)00050-1 [pii] LID - 10.1016/j.exer.2022.108969 [doi] AB - Diabetic retinopathy (DR) represents a major complication of diabetes, and molecular mechanisms related to vascular dysfunction, particularly endothelial dysfunction, in DR remains unclear. In the present work, we generated a DR animal model using mice and a cell model in mouse retinal microvascular endothelial cells (mRMECs) to examine the role of Trefoil factor family 1 (Tff1) in DR. Tff1 was poorly expressed in DR mice and high glucose (HG)-treated mRMECs. Overexpression of Tff1 significantly attenuated streptozotocin-induced retinal proliferation and angiogenesis in DR mice and reduced the secretion of inflammatory factors. In HG-treated mRMECs, overexpression of Tff1 remarkably reduced the proliferation and angiogenesis of mRMECs. In further experiments, we found that Tff1 was transcriptionally repressed by Runt-related transcription factor 1 (Runx1) directly, and Tff1 expression was indirectly modulated by Runx1 via the core-binding factor subunit beta (CBF-beta)/nuclear factor, erythroid 2/microRNA-423-5p axis and the CBF-beta/estrogen receptor 1 (ESR1) axis. Moreover, Tff1 could inhibit the activation of NF-kappaB signaling pathway, which in turn attenuated retinal endothelial cell proliferation and angiogenesis. It was thus proposed that Runx1/Tff1/NF-kappaB axis may be a potential target for the treatment strategy of DR, and further studies are needed. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Zhang, Wei AU - Zhang W AD - Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, PR China; Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, PR China. Electronic address: zhangwei_332@126.com. FAU - Zhang, Dingguo AU - Zhang D AD - Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, PR China. FAU - Cheng, Yan AU - Cheng Y AD - Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China. FAU - Liang, Xing AU - Liang X AD - Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, PR China. FAU - Wang, Jingjing AU - Wang J AD - Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030012, Shanxi, PR China. LA - eng PT - Journal Article DEP - 20220131 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (Core Binding Factor Alpha 2 Subunit) RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) RN - 0 (Runx1 protein, mouse) RN - 0 (Tff1 protein, mouse) RN - 0 (Trefoil Factor-1) SB - IM MH - Animals MH - *Core Binding Factor Alpha 2 Subunit/metabolism MH - *Diabetes Mellitus/metabolism MH - *Diabetic Retinopathy/metabolism MH - Endothelial Cells/metabolism MH - Mice MH - *MicroRNAs/metabolism MH - NF-kappa B/metabolism MH - Neovascularization, Pathologic/metabolism MH - Retina/metabolism MH - *Trefoil Factor-1/metabolism OTO - NOTNLM OT - Diabetic retinopathy OT - Mouse retinal microvascular endothelial cells OT - NF-kappaB signaling pathway OT - Runx1 OT - Tff1 EDAT- 2022/02/04 06:00 MHDA- 2022/04/22 06:00 CRDT- 2022/02/03 20:12 PHST- 2021/09/14 00:00 [received] PHST- 2022/01/25 00:00 [revised] PHST- 2022/01/27 00:00 [accepted] PHST- 2022/02/04 06:00 [pubmed] PHST- 2022/04/22 06:00 [medline] PHST- 2022/02/03 20:12 [entrez] AID - S0014-4835(22)00050-1 [pii] AID - 10.1016/j.exer.2022.108969 [doi] PST - ppublish SO - Exp Eye Res. 2022 Apr;217:108969. doi: 10.1016/j.exer.2022.108969. Epub 2022 Jan 31.