microRNA-221 Inhibits Latent TGF-β1 Activation through Targeting Thrombospondin-1 to Attenuate Kidney Failure-Induced Cardiac Fibrosis
Yue Zhou, Denise Yu En Ng, Mark Richards, Peipei Wang
Abstract
therapeutic efficacy of miR-221 (i.v. 1 mg/kg ×3). miR-221 significantly inhibited Nx-induced upregulation of TSP1 and p-SMAD3 in the heart at day-7 and reduced cardiac fibrosis (picro-sirius), improved cardiac function (±dP/dt), and improved 8-week survival rate (60% versus 36%; p = 0.038). miR-221 mimic treatment improved survival and reduced cardiac fibrosis in a model of severe KF. miR-221 is a therapeutic target to address cardiac fibrosis originating from renal disease and other causes.
Topics & Concepts
Cardiac fibrosismicroRNAFibrosisThrombospondin 1MedicineCancer researchTransforming growth factorKidneyThrombospondinInternal medicineChemistryAngiogenesisMetalloproteinaseBiochemistryGeneMatrix metalloproteinaseChronic Kidney Disease and DiabetesCardiac Fibrosis and RemodelingTissue Engineering and Regenerative Medicine