Effect of hypoxia on proliferation and migration activity of cardiac fibroblasts and its mechanism

  AIM   To investigate the effect of hypoxia on the proliferation and migration activity of neonatal mouse cardiac fibroblasts (CFs) and to explore the underlying mechanism.

  METHODS   C57BL/6J neonatal mouse CFs were isolated, cultured and treated with hypoxia (10 ml/L O₂) and normoxia (210 ml/L O₂). CCK-8 and immunofluorescence method were used to detect the proliferation ability of CFs, light field images were captured for cell migration activity assessment, Western blotting was used to detect changes in related proteins, and drug blocking assay and gene interference were further applied to observe the underlying mechanism.

  RESULTS   Hypoxia treatment significantly promoted CFs proliferation and migration compared with normoxia treatment. Meanwhile, blocking HIF1α by 2-MeOE2 and small interfering RNA (siRNA) targeting HIF1α markedly blunted CFs proliferation and migration, which was in parallel with increased expression of HIF1α after CFs exposed to hypoxia.

  CONCLUSION   Hypoxia promotes the proliferation and migration of CFs via HIF1α, which provides a cue that oxygen deprivation triggers cellular activation of cardiac fibrosis.