<scp>STAT</scp>4 expression and activation is increased during mitosis <i>in vitro</i> and <i>in vivo</i> in skin‐ and mucosa‐derived cell types: implications in neoplastic and inflammatory skin diseases

Ferreli, Caterina; Lai, Chester; August, Suzannah; Buggy, Y.; Kumar, Pawan; Brownlow, Nicola; Parker, Peter J.; Friedmann, Peter S.; Ardern‐Jones, Michael R.; Pickard, C.; Healy, Eugene

doi:10.1111/jdv.14342

Cited by 4 publications

(1 citation statement)

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“…Exaggerated JAK/STAT signaling pathway has been linked to almost every type of autoimmune disease (27). STAT4 functions as a critical factor in the growth of Th1 and in alteration of the balance between Th17 and Tregs in autoimmune diseases (5). Particularly, the targeting relationship between miR-141 and STAT4 has been verified in gastric cancer, and the overexpression of miR-141 has been revealed to play a suppressive role in gastric cancer cell invasion by inhibiting STAT4 (32).…”

Section: Discussionmentioning

confidence: 99%

STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis

Pan

Tan

Wang

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM. NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis.

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Section: Discussionmentioning

confidence: 99%

STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis

Pan

Tan

Wang

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18

Oka

Markova

Tsuzuki

et al. 2020

Cancer Immunol Immunother

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STAT signaling in polycystic kidney disease

Strubl

Torres

Spindt

et al. 2020

Cellular Signalling

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Mutations in the gene coding for the integral membrane protein polycystin-1 (PC1) are the cause of most cases of autosomal-dominant polycystic kidney disease (ADPKD), a very common disease that leads to kidney failure and currently lacks approved treatment. Recent work has revealed that PC1 can regulate the transcription factor STAT3, and that STAT3 is aberrantly activated in the kidneys of ADPKD patients and PKD mouse models. Recent approaches to directly inhibit STAT3 in PKD mouse models have been promising. Numerous signaling pathways are known to activate STAT3 and many have long been implicated in the pathogenesis of PKD-such as EGF/EGFR, HGF/c-Met, Src. However, a role of STAT3 in the pathogenesis of PKD had never been considered until now. Here, we review the current findings that suggest that STAT3 is a promising target for the treatment of PKD. Polycystic Kidney Disease ADPKD is a very common life-threatening, monogenic disease that is characterized by excessive proliferation and the growth of epithelial-lined cysts that eventually destroy the normal renal parenchyma [1, 2]. Most patients eventually progress to renal failure and will require dialysis or kidney transplantation. No approved treatment is currently available to halt or slow disease progression. However, a recent phase 3 trial using a vasopressin V 2receptor antagonist has shown promise in slowing the decline in kidney function [3]. ADPKD is caused by mutations in the PKD1 or PKD2 genes which encode the proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC2 is a calcium channel of the TRP family, and forms a complex with PC1. In addition, PC1-which is mutated in most cases of ADPKD-has been shown to interact with a wide variety of signaling proteins and regulates numerous signaling pathways including heterotrimeric G proteins, wnt-, integrinand JAK/STAT-signaling, and the mTOR pathway. It has remained unclear which of these 1

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STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin‐ and mucosa‐derived cell types: implications in neoplastic and inflammatory skin diseases

Abstract: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

Cited by 4 publications

References 50 publications

STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis

STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis

IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18

STAT signaling in polycystic kidney disease

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