More importantly, HIF-1 signaling mediated pathways, such as the mitogen-activated protein kinase (MAPK) signaling pathway, and the phosphatidylinositol-3-kinase protein kinase B (PI3K-Akt) signaling pathway [89] both directly damaged renal function through contributing to renal fibrosis or proteinuria-induced renal epithelial-mesenchymal transition [90–92]. This evidence concerns the gene AKT1 and renal fibrosis.