In reference previous study, the mRNA levels of HIF-1a, as well as of HIF-1 target genes vegfa, cxcl12, pgk1, were found to be up-regulated upon administration of bleomycin and the development of pulmonary inflammation and fibrosis.[46] As shown in the HIF-1 signaling pathway, growth factor can synthesize HIF-1a via phosphoinositide 3-kinase or mitogen-activated protein kinase (MAPK) pathways. The gene discussed is CXCL12; the disease is inflammation.