Hypoxia related genes modulate in similar fashion in skin fibroblast cells of yak (Bos grunniens) adapted to high altitude and native cows (Bos indicus) adapted to tropical climate during hypoxia stress

Abstract

Abstract The present study was conducted to understand transcriptional response of skin fibroblast of yak (Bos grunniens) and cows of Bos indicus origin to hypoxia stress. Six primary fibroblast cell lines derived from three individuals each of Ladakhi yak (Bos grunniens) and Sahiwal cows (Bos indicus) were exposed to low oxygen concentration for a period of 24h, 48h and 72h. The expression of 10 important genes known to regulate hypoxia response such as HIF1A, VEGFA, EPAS1, ATP1A1, GLUT1, HMOX1, ECE1, TNF-A, GPx and SOD were evaluated in fibroblast cells of Ladakhi yak (LAY-Fb) and Sahiwal cows (SAC-Fb) during pre- and post-hypoxia stress. A panel of 10 reference genes (GAPDH, RPL4, EEF1A1, RPS9, HPRT1, UXT, RPS23, B2M, RPS15, ACTB) were also evaluated for their expression stability to perform accurate normalization. The expression of HIF1A was significantly (p < 0.05) induced in both LAY-Fb (2.29-fold) and SAC-Fb (2.07-fold) after 24h of hypoxia stress. The angiogenic (VEGFA), metabolic (GLUT1) and antioxidant genes (SOD and GPx) were also induced after 24h of hypoxia stress. However, EPAS1 and ATP1A1 induced significantly (p < 0.05) after 48h whereas, ECE1 expression induced significantly (p < 0.05) at 72h after exposure to hypoxia. The TNF-alpha which is a pro-inflammatory gene induced significantly (p < 0.05) at 24h in SAC-Fb and at 72h in LAY-Fb. The induction of hypoxia associated genes indicated the utility of skin derived fibroblast as cellular model to evaluate transcriptome signatures post hypoxia stress in populations adapted to diverse altitudes.