Researchers reported that sumo specific protein 1 (SENP1) plays an important role in the progression of idiopathic pulmonary fibrosis (IPF) and may hence be a potential target for treating the disease. Their findings were published in Cell Communication and Signaling.

Currently, not much is known about the etiology and progression of IPF. Scientists have proposed that the core event driving IPF progression is the proliferation of myofibroblasts induced by chronic injury in the alveolar epithelial cells (AECs).

“The key to IPF treatment is protecting or maintaining the repair and regeneration ability of AECs and inhibiting the accumulation of myofibroblasts,” the authors of the study wrote. 


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Studies have observed that the overexpression of SENP1 is linked to the differentiation of myofibroblasts in lung-resident mesenchymal stem cells. On the other hand, the downregulation of SENP1 in lung-resident mesenchymal stem cells can restore their repair and regenerative function and aid in ameliorating pulmonary fibrosis. 

Read more about IPF etiology 

To investigate this theory, the authors of the study collected lung tissue samples from 6 patients with IPF. In addition, they also obtained pulmonary fibrosis mouse models for their study. The research team also obtained lung-resident mesenchymal stem cells from the lungs of pulmonary fibrosis mouse models.

The researchers discovered that SENP1 was upregulated during myofibroblast differentiation of lung-resident mesenchymal stem cells ex vivo. However, the downregulation of SENP1 managed to inhibit the transformation of lung-resident mesenchymal stem cells into myofibroblasts. This means that the downregulation of SENP1 had the effect of reducing the transformation of lung-resident mesenchymal stem cells into myofibroblasts, preserving their therapeutic properties.

“Maintaining the normal repair function of [mesenchymal stem cells] can prevent the appearance of myofibroblasts,” the research team wrote. “Under normal circumstances, like other [mesenchymal stem cells], [lung-resident mesenchymal stem cells] can maintain lung homeostasis and prevent IPF by repairing damaged lung tissues.” 

Reference

Sun W, Liu X, Yang X, et al. SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progressionCell Commun Signal. 2022;20(1):104. doi:10.1186/s12964-022-00921-4