IFI27, a novel epidermal growth factor‐stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes

Hsieh, Wan-Ling; Huang, Yi; Wang, Tong-Mei; Ming, Yung-Ching; Tsai, Chia-Lung; Pang, Jong‐Hwei S.

doi:10.1111/cpr.12168

Cited by 37 publications

(38 citation statements)

References 54 publications

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“…IFI27 belongs to the family of interferon inducible genes, and recently it has been associated to epidermal proliferation and EGF [6]. In addition, IFI27 was previously identified as a marker of epithelial cancers and psoriatic lesions [10] and related to systemic lupus erythematosus (SLE) [11].…”

Section: Discussionmentioning

confidence: 99%

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Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

et al. 2017

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BackgroundThe IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity.Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection.MethodsWe conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children.ResultsMedian (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r2 = −0.63).ConclusionsThe salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, this gene has recently been associated to the epidermal growth factor (EGF) and involved in proliferation of epithelia [6]. EGF, also known as epithelial growth factor, is a single chain polypeptide secreted by the submandibular salivary glands and other exocrine intestinal glands.…”

Section: Introductionmentioning

confidence: 99%

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

et al. 2017

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“…IFI27 family members also appear to have proapoptotic effects (21,32,34,65,66), possibly as a result of stabilization of the mitochondrial membrane and regulation of caspase activity (21,65). Perhaps because of these proposed pleotropic activities, IFI27 family members have been associated with overexpression in certain cancers (66,67), promotion of skin keratinocyte replication (68), and DNA damage-induced apoptosis and cytochrome c release (21). IFI6-16 (IFI6) is an ISG12 motifcontaining family member that may share some functions with Ifi27l2a.…”

Section: Discussionmentioning

confidence: 99%

The Interferon-Stimulated Gene Ifi27l2a Restricts West Nile Virus Infection and Pathogenesis in a Cell-Type- and Region-Specific Manner

Lucas

Richner

Diamond

2016

J Virol

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The mammalian host responds to viral infections by inducing expression of hundreds of interferon-stimulated genes (ISGs).While the functional significance of many ISGs has yet to be determined, their cell type and temporal nature of expression suggest unique activities against specific pathogens. Using a combination of ectopic expression and gene silencing approaches in cell culture, we previously identified Ifi27l2a as a candidate antiviral ISG within neuronal subsets of the central nervous system (CNS) that restricts infection by West Nile virus (WNV), an encephalitic flavivirus of global concern. To investigate the physiological relevance of Ifi27l2a in the context of viral infection, we generated Ifi27l2a ؊/؊ mice. Although adult mice lacking Ifi27l2a were more vulnerable to lethal WNV infection, the viral burden was greater only within the CNS, particularly in the brain stem, cerebellum, and spinal cord. Within neurons of the cerebellum and brain stem, in the context of WNV infection, a deficiency of Ifi27l2a was associated with less cell death, which likely contributed to sustained viral replication and higher titers in these regions. Infection studies in a primary cell culture revealed that Ifi27l2a ؊/؊ cerebellar granule cell neurons and macrophages but not cerebral cortical neurons, embryonic fibroblasts, or dendritic cells sustained higher levels of WNV infection than wild-type cells and that this difference was greater under conditions of beta interferon (IFN-␤) pretreatment. Collectively, these findings suggest that Ifi27l2a has an antiviral phenotype in subsets of cells and that at least some ISGs have specific inhibitory functions in restricted tissues. IMPORTANCEThe interferon-stimulated Ifi27l2a gene is expressed differentially within the central nervous system upon interferon stimulation or viral infection. Prior studies in cell culture suggested an antiviral role for Ifi27l2a during infection by West Nile virus (WNV). To characterize its antiviral activity in vivo, we generated mice with a targeted gene deletion of Ifi27l2a. Based on extensive virological analyses, we determined that Ifi27l2a protects mice from WNV-induced mortality by contributing to the control of infection of the hindbrain and spinal cord, possibly by regulating cell death of neurons. This antiviral activity was validated in granule cell neurons derived from the cerebellum and in macrophages but was not observed in other cell types. Collectively, these data suggest that Ifi27l2a contributes to innate immune restriction of WNV in a cell-type-and tissue-specific manner. , dengue virus [DENV] and yellow fever virus [YFV]). WNV transmission occurs betweenCulex species mosquitoes and selected avian hosts, with incidental, dead-end infection of horses, humans, and other vertebrate animals. Humans can develop severe disease following WNV infection, as the virus can invade the central nervous system (CNS) and cause flaccid paralysis, meningitis, or encephalitis, often leading to long-term neurological sequelae or death (1)...

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“…IFI27 is suggested to be involved in proliferation of skin keratinocytes [29] and up-regulated in breast cancer, SCC of the skin and ovarian cancer [30–32]. In ovarian cancer IFI27 is associated with patient survival where high IFI27 expression correlates with poor disease free survival [30].…”

Section: Discussionmentioning

confidence: 99%

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

Boldrup

Coates

et al. 2016

Oncotarget

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Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.

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IFI27, a novel epidermal growth factor‐stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes

Abstract: Our study demonstrates for the first time, that cell function of IFI27 is involved in proliferation of skin keratinocytes both in vitro and in vivo. It suggests that IFI27 might be a suitable target for development of a novel anti-psoriasis therapy.

Cited by 37 publications

References 54 publications

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection

The Interferon-Stimulated Gene Ifi27l2a Restricts West Nile Virus Infection and Pathogenesis in a Cell-Type- and Region-Specific Manner

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

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