[The expression of VHL/HIF signaling pathway in the erythroid progenitor cells with chronic mountain sickness]

Objective: To investigate the expression and interaction of VHL/HIF-α pathways including HIF-1α, HIF-2α as well as VHL in erythroid progenitor cells of bone marrow from chronic mountain sickness (CMS) patients. Methods: A total of 25 patients with CMS and 21 healthy controls were recruited for this study. The CD71(+)CD235a(+) cells in bone marrow mononuclear cells, marked as erythroid progenitor cells, were isolated using MACS separation technology. The expression levels of HIF-1α, HIF-2α and VHL in erythroid progenitor cells were detected by Western blotting and real-time fluorescence quantitative PCR. Results: The mRNA levels of HIF-2α were higher in erythroid progenitor cells of CMS than in healthy controls [1.68 (0.81, 2.22) vs 0.98 (0.60, 1.19), P<0.05], while HIF-1α and VHL mRNA levels were similar between the two groups (P>0.05). Spearman analyses indicated that HIF-2α mRNA was positively associated with hemoglobin (Hb) levels in the erythroid progenitor cells of CMS (ρ=0.504, P<0.05). Furthermore, the mRNA level of HIF-2α was correlated with the mRNA level of VHL in the erythroid progenitor cells of CMS (ρ=0.647, P<0.05).The protein levels of HIF-2α in the erythroid progenitor cells of CMS were higher than that of healthy controls [0.94(0.68, 3.30) vs 0.59(0.30, 0.88), P<0.05], but the protein levels of HIF-1α and VHL were similar between the two groups (P>0.05). Conclusions: The abnormal increased expression of HIF-2α in the erythroid progenitor cells of CMS patients leads to the abnormal expression of hypoxia sensitive genes downstream, participating in the occurrence and development of CMS.