Rationale: Etiopathogenesis of IPF is not fully understood, and treatment options are limited. Inhibition of myofibroblast transformation of fibroblasts may be the mechanisms to reverse the formation of fibrosis. Current study shows that the abnormality of circadian rhythm pathway may affect myofibroblast transformation of fibroblasts.
Methods: Lung tissues were collected following bleomycin (BLM)-induced pulmonary fibrosis. The levels of fibrosis-related factors, circadian rhythm pathway per1, per2, per3, bmal, and per2 phosphorylation in the circadian rhythm pathway were measured. Lung fibroblasts with siRNA transfections, adeno-associated virus overexpression or phosphorylation inhibitors of the above factors to determine whether the key circadian rhythm factors affecting the progression of pulmonary fibrosis.
Results: We found a significant upregulation the phosphorylation level of per2 after bleomycin stimulation in mice lung tissue. Overexpression of per1, per2, per3 and siRNA silencing have no significant effect on myofibroblast transformation, while the inhibition of per2 phosphorylation could significantly reduce the myofibroblast transformation of lung fibroblasts.

Conclusions: Our findings implied that Hyperphosphorylation of per2 might be the key factor to promote the progression of pulmonary fibrosis.