title: MicroRNA-155 Promotes the Directional Migration of Resident Smooth Muscle Progenitor Cells by Regulating Monocyte Chemoattractant Protein 1 in Transplant Arteriosclerosis.
abstract: Smooth muscle-like cells are major cell components of transplant arteriosclerosis lesions. This study investigated the origin of the smooth muscle-like cells, the mechanisms responsible for their accumulation in the neointima, and the factors that drive these processes.
  
  
  
  A murine aortic transplantation model was established by transplanting miR-155(-/-) bone marrow cells into miR-155(+/+) mice. MicroRNA-155 was found to play a functional role in the transplant arteriosclerosis. Moreover, we found that the nonbone marrow-derived progenitor cells with markers of both early differentiated smooth muscles and stem cells in the allograft adventitia were smooth muscle progenitor cells. Purified smooth muscle progenitor cells expressed a mature smooth muscle cell marker when induced by platelet-derived growth factor-BB in vitro. In vivo, these cells could migrate into the intima from the adventitia and could contribute to the neointimal hyperplasia. The loss of microRNA-155 in bone marrow-derived cells decreased the concentration gradient of monocyte chemoattractant protein 1 between the intima and the adventitia of the allografts, which reduced the migration of smooth muscle progenitor cells from the adventitia into the neointima.
  
  
  
  This study demonstrated that microRNA-155 promoted the directional migration of smooth muscle progenitor cells from the adventitia by regulating the monocyte chemoattractant protein 1 concentration gradient, which aggravated transplant arteriosclerosis.
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ren
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Anchen
authors.initials: A
authors.lastname: Zhang
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Huang
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Deng
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Chuangyan
authors.initials: C
authors.lastname: Wu
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yue
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Xiangchao
authors.initials: X
authors.lastname: Ding
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China.
authors.forename: Jiuling
authors.initials: J
authors.lastname: Chen
authors.affiliation: From the Department of Vascular Surgery, The Clinical Medical College of Yangzhou University, Yangzhou, China (Y.S., Z.C.); Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Y.S., K.W., J.W., L.R., A.Z., X.H., P.D., C.W., Z.Y., X.D., J.C., J.X.); and Departments of Cardiovascular Medicine (P.Y., L.R., J.X.) and Cardiovascular Surgery (P.Y., L.R., J.X.), Central Hospital of Wuhan, Wuhan, China. jiahong.xia@mail.hust.edu.cn.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xia
mesh_terms: D063194:Adventitia / Q000378:metabolism / Q000473:pathology; D064591:Allografts; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D002633:Chemotaxis; D005838:Genotype; D006965:Hyperplasia; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D058426:Neointima; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D058017:Vascular Grafting / Q000009:adverse effects*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: adventitia; arteriosclerosis; bone marrow; hyperplasia; stem cells