PMID- 32608990 OWN - NLM STAT- MEDLINE DCOM- 20201023 LR - 20201023 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 319 IP - 3 DP - 2020 Sep 1 TI - Upregulating microRNA-874-3p inhibits CXCL12 expression to promote angiogenesis and suppress inflammatory response in ischemic stroke. PG - C579-C588 LID - 10.1152/ajpcell.00001.2020 [doi] AB - Identification of specific biomarkers for ischemic stroke is necessary due to their abilities to improve treatment outcomes. Many studies have demonstrated the involvement of microRNAs (miRNAs) in the pathogenesis and complications of ischemic stroke and patient outcomes. We found that the expression of miR-874-3p was downregulated in clinical samples of ischemic stroke. Thus the present study explored the potential role of miR-874-3p in ischemic stroke and related mechanisms. A mouse model of ischemic stroke was constructed by middle cerebral artery occlusion. The relationship among miR-874-3p, C-X-C motif chemokine ligand 12 (CXCL12), and the Wnt/beta-catenin pathway was explored by dual luciferase reporter assay and Western blot analysis. Angiogenesis and brain tissue apoptosis were evaluated by immunofluorescence staining and TUNEL staining, respectively. ELISA was introduced to measure levels of inflammatory factors, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, IL-8, and IL-10 in brain tissues. Primary hippocampal neuronal cells were isolated from the mouse model of ischemic stroke and incubated with human umbilical vein endothelial cells (HUVECs) for HUVEC tube formation. High expression of CXCL12 and low expression of miR-874-3p were confirmed in ischemic stroke. In addition, miR-874-3p was found to target and downregulate CXCL12, thus reducing TNF-alpha, IL-1, IL-6, and IL-8 levels, but enhancing IL-10 level. Collectively, upregulating miR-874-3p inhibits CXCL12 expression to promote angiogenesis and inhibit inflammation in ischemic stroke mice by activating the Wnt/beta-catenin pathway, which may provide a new direction of ischemic stroke treatment. FAU - Xie, Kangling AU - Xie K AD - Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, People's Republic of China. FAU - Cai, Ying AU - Cai Y AD - Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, People's Republic of China. FAU - Yang, Pu AU - Yang P AD - Department of Vascular Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China. FAU - Du, Feng AU - Du F AD - Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China. AD - Department of Cardiology, The First People's Hospital of Guiyang, Guiyang, People's Republic of China. FAU - Wu, Kai AU - Wu K AD - Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200701 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Chemokine CXCL12) RN - 0 (Cxcl12 protein, mouse) RN - 0 (MIRN874 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Apoptosis/physiology MH - Brain Ischemia/genetics/metabolism MH - Chemokine CXCL12/*metabolism MH - Inflammation/*metabolism MH - Mice MH - MicroRNAs/*genetics MH - Neurons/metabolism MH - Stroke/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Up-Regulation OTO - NOTNLM OT - C-X-C motif chemokine ligand 12 OT - angiogenesis OT - inflammatory factor release OT - ischemic stroke OT - microRNA-874-3p EDAT- 2020/07/02 06:00 MHDA- 2020/10/24 06:00 CRDT- 2020/07/02 06:00 PHST- 2020/07/02 06:00 [pubmed] PHST- 2020/10/24 06:00 [medline] PHST- 2020/07/02 06:00 [entrez] AID - 10.1152/ajpcell.00001.2020 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2020 Sep 1;319(3):C579-C588. doi: 10.1152/ajpcell.00001.2020. Epub 2020 Jul 1.