Open AccessMiR ‐155 inhibits cell migration of human cardiomyocyte progenitor cells ( hCMPC s) via targeting of MMP ‐16
Author(s) -
Liu Jia,
Mil Alain,
Aguor Eissa N. E.,
Siddiqi Sailay,
Vrijsen Krijn,
Jaksani Sridevi,
Metz Corina,
Zhao Jiajun,
Strijkers Gustav J.,
Doevendans Pieter A.,
Sluijter Joost P. G.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01551.x
Subject(s) - cell migration , transfection , progenitor cell , microbiology and biotechnology , microrna , cell , luciferase , endothelial progenitor cell , matrix metalloproteinase , chemistry , biology , stem cell , cell culture , biochemistry , genetics , gene
Undesired cell migration after targeted cell transplantation potentially limits beneficial effects for cardiac regeneration. Micro RNA s are known to be involved in several cellular processes, including cell migration. Here, we attempt to reduce human cardiomyocyte progenitor cell ( hCMPC ) migration via increasing micro RNA ‐155 (miR‐155) levels, and investigate the underlying mechanism. Human cardiomyocyte progenitor cells ( hCMPC s) were transfected with pre‐miR‐155, anti‐miR‐155 or control‐miR (ctrl‐miR), followed by scratch‐ and transwell‐ assays. These functional assays displayed that miR‐155 over‐expression efficiently inhibited cell migration by 38 ± 3.6% and 59 ± 3.7% respectively. Conditioned medium from miR‐155 transfected cells was collected and zymography analysis showed a significant decrease in MMP ‐2 and MMP ‐9 activities. The predicted 3′‐ UTR of MMP ‐16, an activator of MMP ‐2 and ‐9, was cloned into the pMIR ‐ REPORT vector and luciferase assays were performed. Introduction of miR‐155 significantly reduced luciferase activity which could be abolished by cotransfection with anti‐miR‐155 or target site mutagenesis. By using MMP ‐16 si RNA to reduce MMP ‐16 levels or by using an MMP ‐16 blocking antibody, hCMPC migration could be blocked as well. By directly targeting MMP ‐16, miR‐155 efficiently inhibits cell migration via a reduction in MMP ‐2 and ‐9 activities. Our study shows that miR‐155 might be used to improve local retention of hCMPCs after intramyocardial delivery.