IGF-1microRNA与血管疾病-英文课件演示幻灯片.pptVIP

Cell Viability (% Control) Cell Proliferation (% Control) Protein/DNA Ratio (% Control) The Differential effects of ang II in Quiescent and Non-Quiescent Cells Li et al, Am J of Physiol, 2006 290 (5),H2116-23 Ang II increases blood pressure, and produces weight loss and muscle wasting. P= pair fed A= angiotensin II J Clin Invest 2005, 115 (2), 451-458 Generation of skeletal muscle-specific expression of IGF-1 transgenic mice. Skeletal muscle-specific expression of IGF-1 prevents ang II induced muscle weight loss (preferential in fast-fiber, not in slow fiber) Tg= transgenic WT= wild type J Clin Invest 2005, 115 (2), 451-458 Skeletal muscle-specific expression of IGF-1 prevents ang II induced muscle weight loss through pAkt. Tg= transgenic WT= wild type J Clin Invest 2005, 115 (2), 451-458 Ang II-induced muscle loss is associated with reduced levels of pBad, increased cytochrome C release into the cytosolic fraction, and DNA fragmentation. Gastrocnemius lysates were used. J Clin Invest 2005, 115 (2), 451-458 Ang II IGF-1 Akt Caspase-3 Actin cleavage Protein degradation Apoptosis Atrophy AT1R microRNA155 IGF-1, Angiotensin II and AT1R Bioinformatic analyses of microRNA155 that may target AT1R miRanda TargetScan miR155 miR155 ΔG Analysis (-kcal/mol) of the 70 nucleotides flanking the 5’ and 3’ of AT1R 3’ UTR regions 5’70 bp ΔG = -10.4 3’70 bp ΔG = -9.0 IGF-1, miR-155 and AT1R Methods: mirVana miRNA isolation mirVana qRT-PCR miRNA Detection 5S rRNA as control. Results: IGF-1 increase miR155 expression, and decrease AT1R expression in VSMC. Has-miR-206::IGF-1 Complementary IGF1 (NM_000618) Position 151-158 of IGF1 3’UTR 5’ …GAAAUACACAAGUAAACAUUCCA… 3’ … GGUGUGUGAAGGAAUGUAAGGU… Has-miR-1::IGF-1 Complementary IGF1 (NM_000618) Position 151-158 of IGF1 3’UTR 5’ …GAAAUACACAAGUAAACAUUCCA… 3’ …AUGUAUGAAGAAA-- UGUAAGGU miRNA IGF-1 IGF-1R miR-1 + miR-206 + miR-613 + miR-409 + miR-217 + Bioinformatic analyses of miRNA that may target IGF-1 and IGF-1R Website