The level of expression of 2 genes—interferon-induced protein 44-like (IFI44L) and signal transducer and activator of transcription 1 (STAT1)—are higher in the lung tissues of a rat model with pulmonary arterial hypertension (PAH), compared with controls. This finding is based on an analysis conducted by a team of researchers in China. 

“Our findings reveal the novel pathological mechanisms underlying PAH and indicate that STAT1 and IFI44L may represent potential therapeutic targets in PAH,” the researchers wrote in their paper published in Bioengineered.

A better understanding of the biological mechanisms and key genes involved in PAH pathogenesis could help develop new therapies for this disease, which has a high mortality rate.

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In the present study, the team led by Jing Yuan used integrated weighted gene coexpression network analysis to find networks and modules in PAH that were most relevant. Their aim was to examine the biological mechanisms underlying the disease and identify key genes that can be used as clinical biomarkers to find new therapeutic targets.

After identifying clinically relevant modules, the researchers performed a functional enrichment analysis and found 7 key genes in lung samples from patients with PAH. These genes were related to inflammation, autoimmunity, and endothelial cell differentiation. The 2 genes IFI44L and STAT1 were expressed at higher levels in the lung tissue of a rat model of PAH. 

These 2 genes could be used as novel biomarkers of PAH, the team concluded. However, the expression in lung tissue of PAH patients must first be validated.

IFI44L is thought to be involved in inflammation, autoimmune disorders, and cancer. Recent studies have shown that it may be a tumor suppressor gene that regulates cancer stemness and metastasis in hepatocellular carcinoma.

STAT1 encodes for a nuclear transcription factor that is involved in the cell cycle, apoptosis, and immune responses.

Reference

Yang H, Lu Y, Yang H, et al. Integrated weighted gene co-expression network analysis uncovers STAT1(signal transducer and activator of transcription 1) and IFI44L (interferon-induced protein 44-like) as key genes in pulmonary arterial hypertension. Bioengineered. 2021;12(1):6021-6034. doi:10.1080/21655979.2021.1972200

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