PMID- 29332916 OWN - NLM STAT- MEDLINE DCOM- 20180206 LR - 20180206 IS - 1349-3299 (Electronic) IS - 1349-2365 (Linking) VI - 59 IP - 1 DP - 2018 Jan 27 TI - MiR-135a Promotes Inflammatory Responses of Vascular Smooth Muscle Cells From db/db Mice via Downregulation of FOXO1. PG - 170-179 LID - 10.1536/ihj.17-040 [doi] AB - It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC. On the other hand, transfection of an miR-135a inhibitor reversed the activated interaction between monocytes and db/db VSMC. The pro-inflammatory responses could also be enhanced by using siRNAs to silence the FOXO1 gene in WT VSMC, suggesting a negative regulatory role of FOXO1. FOXO1 siRNAs and miR-135a mimics could both enhance the transcriptional activity of COX-2 promoter. Using chromatin immunoprecipitation, we found that in db/db VSMC, the occupancy in promoter regions of inflammatory genes by FOXO1 was reduced.miR-135a increased the inflammatory responses of VSMC involved in complications of vascular diseases by downregulating the expression of FOXO1. FAU - Lu, Xiaochun AU - Lu X AD - Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital. FAU - Yin, Dawei AU - Yin D AD - Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital. FAU - Zhou, Bo AU - Zhou B AD - Department of Geriatrics, the Affiliated Zhongda Hospital of Southeast University. FAU - Li, Tieling AU - Li T AD - Department of Cadre Clinic, Chinese People's Liberation Army General Hospital. LA - eng PT - Comparative Study PT - Journal Article DEP - 20180115 PL - Japan TA - Int Heart J JT - International heart journal JID - 101244240 RN - 0 (Forkhead Box Protein O1) RN - 0 (Foxo1 protein, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn135 microRNA, mouse) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - DNA/genetics MH - Disease Models, Animal MH - *Down-Regulation MH - Forkhead Box Protein O1/biosynthesis/*genetics MH - *Gene Expression Regulation MH - Immunohistochemistry MH - Inflammation/*genetics/metabolism/pathology MH - Male MH - Mice MH - Mice, Knockout MH - MicroRNAs/biosynthesis/*genetics MH - Myocytes, Smooth Muscle/*metabolism/pathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Vascular Diseases/*genetics/metabolism/pathology OTO - NOTNLM OT - COX-2 OT - MCP-1 OT - Pro-inflammatory OT - Vascular disease EDAT- 2018/01/16 06:00 MHDA- 2018/02/07 06:00 CRDT- 2018/01/16 06:00 PHST- 2018/01/16 06:00 [pubmed] PHST- 2018/02/07 06:00 [medline] PHST- 2018/01/16 06:00 [entrez] AID - 10.1536/ihj.17-040 [doi] PST - ppublish SO - Int Heart J. 2018 Jan 27;59(1):170-179. doi: 10.1536/ihj.17-040. Epub 2018 Jan 15.