Suppression of growth factor expression and human vascular smooth muscle cell growth by small interfering RNA targeting EGR-1.
Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the reparative response to injury after percutaneous coronary intervention and in failed bypass grafts for the treatment of atherosclerosis. In the present study, we generated novel synthetic small interfering RNA (siRNA) molecules targeting the coding region of human early growth response-1 (EGR-1) mRNA that attenuate the expression of EGR-1 and that of fibroblast growth factor-2 (FGF-2) and granulocyte-colony stimulating factor (G-CSF). These agents suppressed SMC proliferation in a dose-dependent and non-toxic manner and blocked SMC regrowth from the wound edge following mechanical injury in vitro. In contrast, the scrambled counterpart did not inhibit SMC proliferation, EGR-1 protein expression or SMC regrowth after injury. These findings demonstrate that EGR-1 siRNA can serve as inhibitors of SMC proliferation and wound repair suggesting that these agents may potentially be useful in the control of vascular proliferative disorders.
Fahmy
Roger G
RG
Department of Pathology, Centre for Vascular Research, The University of New South Wales, Sydney, Australia.
Khachigian
Levon M
LM
D000818:Animals; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor