microRNA‐ 107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1‐dependent Notch signaling pathway in a mouse model of coronary atherosclerosis
Authors: Xiao-Lin Ji
Jie Gu
Zhi-Feng Gao
Lin Ding
Huan Zhang
Xiao-Yu Wang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: KRT1; Notch signaling pathway; coronary atherosclerosis; inflammatory response; microRNA-107
Affiliations: Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, P.R. China., Department of Anesthesiology, Peking University International Hospital, Beijing, P.R. China.

Abstract:  Coronary atherosclerosis is a long-term, sustained, and evolving inflammatory disease manifested with the remodeling of the coronary arteries. The purpose of this study is to explore the potential role of microRNA-107 (miR-107) in vascular endothelial cells (VECs) in coronary atherosclerosis by regulating the KRT1 gene and the Notch signaling pathway. A mouse model of coronary atherosclerosis was established. The relationship between miR-107 and KRT1 was analyzed and verified by dual-luciferase reporter assay. The functional role of miR-107 in coronary atherosclerosis was determined using ectopic expression and depletion. Blood lipid levels and atherosclerotic index (AI) were measured in atherosclerotic mice. Expression pattern of miR-107, KRT1, Notch signaling pathway, inflammatory/anti-inflammatory factors, and endoplasmic reticulum (ER) stress-related genes was evaluated by means of reverse transcription quantitative polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Meanwhile, cell-cycle distribution and cell apoptosis in VECs were assessed by flow cytometry. Atherosclerotic mice exhibited higher blood lipid levels, AI, apoptotic index, and KRT1-positive expression as well as inhibited Notch signaling pathway when compared with normal mice. The miR-107 was revealed to bind to KRT1; miR-107 upregulation or KRT1 silencing resulted in reductions in blood lipid levels and AI, inhibition in cell apoptosis, inflammation, and ER stress. Restored miR-107 or downregulated KRT1 activated the Notch signaling pathway. These results supported the notion that miR-107-targeted KRT1 inhibition activated the Notch pathway, thereby, protecting against the coronary atherosclerosis. Findings in this study might provide a novel biomarker for the coronary atherosclerosis treatment. 

Retracted: No

PubPeer comments:
 Fig 8(a)  Upregulated miRu2010107 or downregulated KRT1 promotes cell cycle progression and inhibits apoptosis. (a) Cellu2010cycle distribution determined by flow cytometry. ![file] Inquiring minds would like to know more about the software involved in plotting this figure. My understanding is that one of the black lines is the raw data, a histogram of cell counts against protein level, while the other is the best fit to that raw data produced by a combination of the striped-hump and red-peak templates. ![file] How do raw-data histograms have overhangs? How do best-fit combinations have weird undulations? ,