Expression of suppressor of cytokine signaling 1 (SOCS1) gene dramatically increases in relapsing–remitting multiple sclerosis

Kakhki, Majid Pahlevan; Rakhshi, Nahid; Heidary, Masoumeh; Behmanesh, Mehrdad; Nikravesh, Abbas

doi:10.1016/j.jns.2015.02.005

Cited by 15 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, the SOCS proteins affect the duration and intensity of cytokine signals and the defective expression of SOCS-1 and SOCS-3 that have been shown in a lot of human diseases (Yu et al, 2011). SOCS-1 is a vital regulator in cytokines signaling, playing the most significant role in the modulation of autoimmune responses (Pahlevan Kakhki, Rakhshi, Heidary, Behmanesh, & Nikravesh, 2015). The JAK/STAT signaling pathway is critical for many kinds of cytokines and growth factors (Wang, Zhang, Dui, Ren, & Liu, 2016).…”

Section: Introductionmentioning

confidence: 99%

microRNA‐30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS‐1 in rats with sepsis

Yuan

Chen

Zhao

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Sepsis is a systemic inflammatory response that may be induced by trauma, infection, surgery, and burns. With the aim of discovering novel treatment targets for sepsis, this current study was conducted to investigate the effect and potential mechanism by which microRNA‐30a (miR‐30a) controls sepsis‐induced liver cell proliferation and apoptosis. Rat models of sepsis were established by applying the cecal ligation and puncture (CLP) method to simulate sepsis models. The binding site between miR‐30a and suppressor of cytokine signaling protein 1 (SOCS‐1) was determined by dual luciferase reporter gene assay. The gain‐of‐and‐loss‐of‐function experiments were applied to analyze the effects of miR‐30a and SOCS‐1 on liver cell proliferation and apoptosis of the established sepsis rat models. The expression of miR‐30a, SOCS‐1, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Bcl‐2 associated X protein (Bax), B cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), and high‐mobility group box 1 (HMGB1), and the extent of JAK2 and STAT3 phosphorylation were all determined. Sepsis led to an elevation of miR‐30a and also a decline of SOCS‐1 in the liver cells. SOCS‐1 was negatively regulated by miR‐30a. Upregulated miR‐30a and downregulated SOCS‐1 increased the expression of JAK2, STAT3, Bax, TLR4, and HMGB1 as well as the extent of JAK2 and STAT3 phosphorylation whereas impeding the expression of SOCS‐1 and Bcl‐2. More important, either miR‐30a elevation or SOCS‐1 silencing suppressed liver cell proliferation and also promoted apoptosis. On the contrary, the inhibition of miR‐30a exhibited the opposite effects. Altogether, we come to the conclusion that miR‐30a inhibited the liver cell proliferation and promoted cell apoptosis by targeting and negatively regulating SOCS‐1 via the JAK/STAT signaling pathway in rats with sepsis.

show abstract

Section: Introductionmentioning

confidence: 99%

microRNA‐30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS‐1 in rats with sepsis

Yuan

Chen

Zhao

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…SOCS1, a negative modulator of cytokine signaling, is important for immune cell homeostasis and the regulation of inflammation [23,24]. Gene variants in the 5' untranslated region (UTR) of SOCS1 (rs243324 and rs441349) have been identified in cytokine pathway gene screenings as multiple sclerosis (MS) susceptibility variants [19,25]. Many questions still remain unanswered regarding the specific molecular mechanisms and tissue-specific contributions by which CLEC16A contributes to autoimmunity.…”

Section: Clec16a (16p13)-an Autoimmune Candidate Genementioning

confidence: 99%

CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration

Pandey

Bakay

Hákonarson

2023

IJMS

View full text Add to dashboard Cite

CLEC16A is emerging as an important genetic risk factor for several autoimmune disorders and for Parkinson disease (PD), opening new avenues for translational research and therapeutic devel-opment. While the exact role of CLEC16A in health and disease is still being elucidated, the gene plays a critical role in the regulation of autophagy, mitophagy, endocytosis, intracellular trafficking, immune function, and in biological processes such as insulin secretion and others that are important to cellular homeostasis. As shown in both human and animal modeling studies, CLEC16A hypo-function predisposes to both autoinflammatory phenotype and neurodegeneration. While the two are clearly related, further functional studies are needed to fully understand the mechanisms in-volved for optimized therapeutic interventions. Based on recent data, mitophagy-inducing drugs may be warranted, and such therapy should be tested in clinical trials as these drugs would tackle the underlying pathogenic mechanism (s) and could treat or prevent symptoms of autoimmunity and neurodegeneration in individuals with CLEC16A risk variants. Accordingly, interventions di-rected at reversing the dysregulated mitophagy and the consequences of loss of function of CLEC16A without activating other detrimental cellular pathways could present an effective ther-apy. This review presents the emerging role of CLEC16A in health and disease and provides an update on the disease processes that are attributed to variants located in the CLEC16A gene, which are responsible for autoimmune disorders and neurodegeneration with emphasis on how this in-formation is being translated into practical and effective applications in the clinic.

show abstract

“…In general, SOCS genes are important in the regulation of cytokine signaling and autoimmune responses through the JAK/STAT pathway. 145–147 SOCS1 plays a role in the regulation of immune cell homeostasis as well as in inflammation. 148 SOCS1 suppresses DC activity by inhibition of STAT1, which normally activates DCs.…”

Section: Suppressor Of Cytokine Signaling and Its Association With Msmentioning

confidence: 99%

Involvement of Immune Regulation in Multiple Sclerosis

Spagnuolo

Piavis

Williams

2017

Immunol Immunogenet Insights

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a neurodegenerative disease characterized by neuroinflammation and demyelination that results in axon loss. Multiple sclerosis has been shown to be the result of an autoimmune response caused by a mixture of genetic and environmental factors. Dendritic cells are prominent antigen-presenting cells that interact with various molecules to regulate the immune system. The dysfunction of various features of immune regulation, including interleukins (ILs), CD4 + T cells, and suppressor of cytokine signaling (SOCS1), has been implicated in the pathogenesis of MS. T cells, particularly through the malfunction of B7-costimulatory pathways, have been shown to affect the progression of the disease. SOCS1 is important in regulating the function of T cells through its interactions with other nearby genes, especially CLEC16A, with abnormal decreases in SOCS1 expression leading to the exhibition of MS symptoms. The activation of IL-23 receptors on CD4 + T cells is pivotal to their differentiation into pathogenic T H 17 cells. Several promising compounds that downregulate gene expression of IL-23 and IL-23R have been discovered but require further investigation for efficacy and safety. Given their role in the severity and progression of MS, therapies that decrease these dysregulations may ultimately decrease symptoms and in turn improve patients' quality of life.

show abstract

Expression of suppressor of cytokine signaling 1 (SOCS1) gene dramatically increases in relapsing–remitting multiple sclerosis

Cited by 15 publications

References 34 publications

microRNA‐30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS‐1 in rats with sepsis

microRNA‐30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS‐1 in rats with sepsis

CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration

Involvement of Immune Regulation in Multiple Sclerosis

Contact Info

Product

Resources

About