Fig 1: Local GHR regulates mitochondrial biogenesis via IGF1-PI3K/AKT/CREB pathway. a The PPI network of human GHR, IGF1, AKT, CREB and PGC1a. b The PPI network of mouse GHR, IGF1, AKT, CREB and PGC1a. c The PPI network of pig GHR, IGF1, AKT, CREB and PGC1a. d The PPI network of chicken GHR, IGF1, AKT, CREB and PGC1a. Protein–protein interaction was performed by the String database and visualized by Cytoscape (version 3.4.0). e and f Western blots with anti-JAK2, anti-p-JAK2, anti-AKT1, anti-p-AKT1, anti-CREB1, anti-p-CREB1 and anti-ß-actin at 48 h after transfection with si-GHR and si-NC. g and h Western blots with anti-AKT1, anti-p-AKT1, anti-CREB1, anti-p-CREB1 and anti-ß-actin at 48 h after transfection with si-IGF1 and si-NC. i and j Western blots with anti-AKT1, anti-p-AKT1, anti-CREB1, anti-p-CREB1 and anti-ß-actin at 48 h after co-transfection with si-GHR + pcDNA3.1-IGF1, si-GHR + pcDNA3.1 and si-NC + pcDNA3.1. k LY294002 (PI3K inhibitor) was added at 24 h before measuring the expression of PGC1a by RT-qPCR at 48 h after transfection of pcDNA3.1-IGF1 and pcDNA3.1. l GSK690693 (AKT inhibitor) was added at 24 h before measuring the expression of PGC1a by RT-qPCR at 48 h after transfection of pcDNA3.1-IGF1 and pcDNA3.1. m and n LY294002 or GSK690693 was added at 24 h before measuring the protein levels with anti-PGC1a, anti-CREB1, anti-p-CREB1 and anti-ß-actin at 48 h after transfection of pcDNA3.1-IGF1 and pcDNA3.1. o The expression of CREB and PGC1a was measured by RT-qPCR at 48 h after transfection with pcDNA3.1-CREB and pcDNA3.1. p and q Western blots with anti-PGC1a, anti-CREB1, anti-p-CREB1 and anti-ß-actin at 48 h after transfection with pcDNA3.1-CREB and pcDNA3.1. r Dual-Luciferase report assays transfected with reporter vectors containing different length of 5' upstream region of PGC1a. s Dual-Luciferase report assays of CREB overexpression co-transfected with reporter vectors containing different length of 5' upstream region of PGC1a. Data are shown as mean ± SEM, *p < 0.05, **p < 0.01