Interferon regulatory factor 9 plays a dual function in health and disease
Authors: Wei-Li Yu, Yun Sun
Journal: Journal of Hepatology (2015)

Interferon regulatory factor 9 is a key mediator of hepatic ischemia/reperfusion injuryJournal of HepatologyVol. 62Issue 1PreviewLiver ischemia and reperfusion (I/R) injuries arising from transplantation, trauma, or hypovolemic shock may cause liver failure or even multi-organ system failure [1]. Because cell death has long been viewed as a fundamental process that directly determines the extent of liver function damage in I/R injury, hepatocyte protection is a potential strategy for ameliorating I/R liver damage [2,3]. However, anti-apoptotic approaches are not widely used in existing therapies for liver I/R [4]. One possible reason is that the upstream mediators remain poorly defined in hepatocytes, even though considerable attention has been focused on apoptotic pathways [5]. Full-Text PDF Reply to: “Interferon regulatory factor 9 plays a dual function in health and disease”Journal of HepatologyVol. 62Issue 6PreviewWe appreciate Yu and Sun for their comments on our recent findings, which focused on the dual functions of interferon (IFN) regulatory factor 9 (IRF9) on cardiometabolic diseases. Full-Text PDF Open Access Interferon regulatory factor 9 (IRF9), as interferon-stimulated gene factor 3 gamma (ISGF3G), belongs to the IRF family and participates in a series of molecular pathways related to cell proliferation, oncogenesis, apoptosis, and innate immunity. IRF9 not only acts as a transcription factor, but also interacts with other transcription factors to regulate gene expression. However, IRF9 has a dual role in health and disease. Recently, the article by Wang et al. [[1]Wang P.X. Zhang R. Huang L. Zhu L.H. Jiang D.S. Chen H.Z. et al.Interferon regulatory factor 9 is a key mediator of hepatic ischemia/reperfusion injury.J Hepatol. 2014; 62: 111-120Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar] showed that IRF9 overexpression aggravated the hepatic ischemia/reperfusion (I/R) injury and its deficiency significantly mitigated the symptoms after liver I/R. The results demonstrated that IRF9 induced hepatocyte apoptosis after I/R injury. Moreover, the paper by Zhang et al. [[2]Zhang S.M. Zhu L.H. Chen H.Z. Zhang R. Zhang P. Jiang D.S. et al.Interferon regulatory factor 9 is critical for neointima formation following vascular injury.Nat Commun. 2014; 5: 5160Crossref PubMed Scopus (48) Google Scholar] indicated that IRF9 deletion suppressed the proliferation and migration of vascular smooth muscle cells (VSMC) and ameliorated intimal thickening. In contrast, IRF9 gain-of-function promoted VSMC proliferation and migration and aggravated arterial narrowing. Furthermore, the article by Chen et al. [[3]Chen H.Z. Guo S. Li Z.Z. Lu Y. Jiang D.S. Zhang R. et al.A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.J Neurosci. 2014; 34: 11897-11912Crossref PubMed Scopus (48) Google Scholar] showed that IRF9 accumulated in neurons in response to I/R and IRF9 deficiency markedly attenuated both post-stroke neuronal death and neurological deficits. By comparison, IRF9 overexpression in neurons resulted in affected neurons to die. In addition, Zhang et al. [[4]Zhang Y. Liu X. She Z.G. Jiang D.S. Wan N. Xia H. et al.Interferon regulatory factor 9 is an essential mediator of heart dysfunction and cell death following myocardial ischemia/reperfusion injury.Basic Res Cardiol. 2014; 109: 434Crossref PubMed Scopus (44) Google Scholar] indicated that IRF9 upregulation was found in human ischemic heart tissue and mouse hearts after I/R injury. Furthermore, IRF9 deficiency protected the heart against I/R-induced cardiomyocyte death, inflammation, and dysfunction. Whereas, IRF9 overexpression in cardiomyocyte aggravated myocardial reperfusion injury and inflammation. From the above data, IRF9 was suggested as a negative regulator in the suppression of I/R injury, arterial narrowing, post-stroke neuronal death and neurological deficits. However, the article by Jiang et al. [[5]Jiang D.S. Luo Y.X. Zhang R. Zhang X.D. Chen H.Z. Zhang Y. et al.Interferon regulatory factor 9 protects against cardiac hypertrophy by targeting myocardin.Hypertension. 2014; 63: 119-127Crossref PubMed Scopus (70) Google Scholar] showed that IRF9 deficiency presented marked cardiac hypertrophy and IRF9 overexpression exhibited the decrease of hypertrophic response. The results demonstrated that IRF9 suppressed the development of cardiac hypertrophy. It indicated that IRF9 played a positive role in the inhibition of cardiac hypertrophy. Together, these findings suggested that IRF9 not only acted as a negative regulator, but also a suppressor in health and disease, such as I/R injury, arterial narrowing, post-stroke neuronal death and neurological deficits, and cardiac hypertrophy. We read with interest the article by Wang et al. and thought that IRF9 may play a dual function in health and disease. This work was supported by Anhui Provincial Natural Science Foundation (Grant No. 1508085qc49), the school foundation project of Anhui Medical University (Grant No. 2015xkj031) and the doctoral research foundation project of the Second Affiliated Hospital of Anhui Medical University (Grant No. 2014bkj034). The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.