A new role of endoplasmic reticulum stress in idiopathic pulmonary fibrosis (IPF) was revealed in a study published in Stem Cell Research & Therapy.

According to the study, endoplasmic reticulum stress influences the fate of lung resident mesenchymal/stromal cells through the stress responder C/EBP homologous protein (CHOP) and induces fibrosis. These results suggest that targeting CHOP could be a novel therapeutic avenue for IPF.

To investigate the potential role of endoplasmic reticulum stress on the behavior of lung resident mesenchymal/stromal cells during pulmonary fibrosis in IPF, a team of researchers from China evaluated these processes in patients with IPF. The team also used primary mouse lung resident mesenchymal/stromal cells to test the effects of endoplasmic reticulum stress and CHOP on these cells.


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The results showed that myofibroblast differentiation was associated with endoplasmic reticulum stress in the lungs of patients with IPF.

Read more about the etiology of IPF

The team also found that when they induced endoplasmic reticulum stress in the mouse cells using tunicamycin, the paracrine, migration, and reparative functions of lung resident mesenchymal/stromal cells were impaired. 

When they overexpressed CHOP, the myofibroblast transformation of lung resident mesenchymal/stromal cells induced by transforming growth factor (TGF) β1 was facilitated. 

On the contrary, when they knocked down CHOP in the mice, the researchers found that engraftment was facilitated and myofibroblast transformation was inhibited, thereby promoting the efficacy of adopted lung resident mesenchymal/stromal cells in alleviating pulmonary fibrosis.

The researchers concluded that therapies targeting and modifying the function of lung resident mesenchymal/stromal cells may help treat pulmonary fibrosis.

IPF is a progressive lung disease of unknown etiology characterized by the buildup of fibrotic tissue in the pulmonary parenchyma. The incidence of the disease varies greatly. This could be due to factors that reduce the epithelial repair of lung resident mesenchymal/stromal cells, such as smoking and agricultural organic dust.

Reference

Yang X, Sun W, Jing X, Zhang Q, Huang H, Xu Z. Endoplasmic reticulum stress modulates the fate of lung resident mesenchymal stem cell to myofibroblast via C/EBP homologous protein during pulmonary fibrosis. Stem Cell Res Ther. 2022;13(1):279. doi:10.1186/s13287-022-02966-1