SH2 superbinder has significant antifibrotic effects, according to a new study published in Theranostics. The protein could therefore be used as a promising therapy for idiopathic pulmonary fibrosis (IPF), the authors of the study said.

There is currently no effective treatment for IPF, so it is of great importance to developing new and better treatments for the disease.

Although the exact etiology of the disease is not fully understood, it is known that IPF develops as the result of alveolar epithelial type 2 cell injury, and the abnormal proliferation, migration, and differentiation of pulmonary fibroblasts. The activation of phosphotyrosine-mediated signaling pathways may also be involved in the pathophysiology of the disease.


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Here, a team of researchers from China explored the potential of SH2 superbinder, which has been shown to be able to block the phosphotyrosine pathway, as a therapy for IPF. They first examined phosphotyrosine levels in the lung tissue of patients with IPF. They found that cytokine and growth factor pathways, which directly correlated with levels of phosphotyrosine were significantly higher in IPF.

Read more about the etiology of IPF

The team also analyzed cell proliferation, migration, and differentiation associated with phosphotyrosine in a mouse model of pulmonary fibrosis. “High [phosphotyrosine] levels were found to induce abnormal proliferation, migration, and differentiation of lung fibroblasts,” they wrote.

Finally, the researchers investigated the antifibrotic effects as well as the safety and effectiveness of SH2 superbinder in the mice. They reported that SH2 superbinder blocked phosphotyrosine-mediated signaling pathways and inhibited lung fibrosis.

When they compared the antifibrotic and side-effect of SH2 superbinder to those of nintedanib, a treatment approved by the US Food and Drug Administration for the treatment of IPF, the researchers found that SH2 superbinder had better therapeutic effects and fewer side effects in the animals.

SH2 superbinder is a protein that was first created by Kaneko and colleagues in 2012. It contains 3 amino acid changes, which increases its affinity for phosphotyrosine. The SH2 superbinder used in this study also contains a modification that increases its ability to cross cellular membranes and access intracellular targets.

Reference

Wang M, Liu AD, Niu Q, et al. Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis. Theranostics. 2022;26;12(10):4513-4535. doi:10.7150/thno.72269