STAT3: A key regulator in liver fibrosis

Zhao, Jie; Qi, Yongfen; Yu, Yan-Rong

doi:10.1016/j.aohep.2020.06.010

Cited by 112 publications

(64 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stat 3 has been shown to be activated by gamma radiation in vitro [ 71 ]. In addition, upregulation of Stat3 has been shown to have both anti- and pro-inflammatory roles during the pathogenesis of liver fibrosis [ 72 ]. c-myc has been linked with both ROS formation and DNA damage [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Perturbed transcriptional profiles after chronic low dose rate radiation in mice

et al. 2021

View full text Add to dashboard Cite

Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. There is a lack of relevant low dose rate data that is partly ascribed to the rarity of exposure facilities allowing chronic low dose rate exposures. Using the FIGARO facility, we assessed early (one day post-radiation) and late (recovery time of 100–200 days) hepatic genome-wide transcriptional profiles in male mice of two strains (CBA/CaOlaHsd and C57BL/6NHsd) exposed chronically to a low dose rate (2.5 mGy/h; 1200h, LDR), a mid-dose rate (10 mGy/h; 300h, MDR) and acutely to a high dose rate (100 mGy/h; 30h, HDR) of gamma irradiation, given to an equivalent total dose of 3 Gy. Dose-rate and strain-specific transcriptional responses were identified. Differently modulated transcriptional responses across all dose rate exposure groups were evident by the representation of functional biological pathways. Evidence of changed epigenetic regulation (global DNA methylation) was not detected. A period of recovery markedly reduced the number of differentially expressed genes. Using enrichment analysis to identify the functional significance of the modulated genes, perturbed signaling pathways associated with both cancer and non-cancer effects were observed, such as lipid metabolism and inflammation. These pathways were seen after chronic low dose rate and were not restricted to the acute high dose rate exposure. The transcriptional response induced by chronic low dose rate ionizing radiation suggests contribution to conditions such as cardiovascular diseases. We contribute with novel genome wide transcriptional data highlighting dose-rate-specific radiation responses and emphasize the importance of considering both dose rate, duration of exposure, and variability in susceptibility when assessing risks from ionizing radiation.

show abstract

Section: Discussionmentioning

confidence: 99%

Perturbed transcriptional profiles after chronic low dose rate radiation in mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A concern regarding this newly developed method is that the quality of stem cells from old individuals and patients with severe inflammation may be low (38)(39)(40). STAT3 is a transcription factor belonging to the STAT protein family (41,42) that is activated by inflammatory cytokines, including in diseases associated with chronic inflammation and fibrosis (42)(43)(44)(45)(46)(47). The restoration of stem cell function by STAT3 signaling inhibition has been previously evaluated (48)(49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates

Lee¹,

Kim²,

Go³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Venous blood drained from the knee joint after total knee arthroplasty (TKA) using a hemovac line is a potential source of bone marrow components, including stem cells, from the cutting surface of cancellous bones of the knee joint. However, the function of mesenchymal stem cells (MSCs) in patients with osteoarthritis (OA-MSCs) can be disrupted by inflammation of the joint. Further, to override the invasive nature of the currently used methods to obtain stem cells, their functional modification is necessary for therapeutic applications. Methods: The effects of signal transducer and activator of transcription 3 (STAT3) signaling suppression on MSCs (iSTAT3-MSCs) were evaluated by comparative analyses of the characteristics of OA-MSCs and iSTAT3-MSCs from 20 patients who underwent TKA.Results: OA-MSCs and iSTAT3-MSCs were adherent, with fibroblast-like appearance and high rates of expression of MSC-specific markers, including CD73, CD90, and CD105 (>90%). Both OA-MSCs and iSTAT3-MSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic cells; however, iSTAT3-MSCs showed higher levels of osteogenic and chondrogenic differentiation markers than OA-MSCs. Additionally, the anti-inflammatory and chondroprotective cytokine levels were higher in iSTAT3-MSCs than in OA-MSCs.Conclusions: These findings indicate that iSTAT3-MSCs after TKA are potentially effective for stem cell therapy in the context of bone and cartilage disorders.

show abstract

“…In recent years, series of studies have provided evidence that the JAK/STAT signaling pathway is closely related to the occurrence and development of liver fibrosis and HCC caused by HBV (164). Some experiments have documented that H3K27ac and H3K4me3 expression modification (active gene transcription hallmarkers), and circSOD2 expression were further increased after histone writer EP300 and WDR5 binding to circSOD2 promoter.…”

Section: Several Critical Cell Signaling Pathways Regulated By Circrnas In Hbv-hccmentioning

confidence: 99%

Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma

et al. 2021

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are newly classified noncoding RNA (ncRNA) members with a covalently closed continuous loop structure that are involved in immune responses against hepatitis B virus (HBV) infections and play important biological roles in the occurrence and pathogenesis of HCC progression. The roles of circRNAs in HBV-associated HCC (HBV-HCC) have gained increasing attention. Substantial evidence has revealed that both tissue and circulating circRNAs may serve as potential biomarkers for diagnostic, prognostic and therapeutic purposes. So far, at least four circRNA/miRNA regulatory axes such as circRNA_101764/miR-181, circRNA_100338/miR-141-3p, circ-ARL3/miR-1305, circ-ATP5H/miR-138-5p, and several circulating circRNAs were reported to be associated with HBV-HCC development. Notably, TGF/SMAD, JAK/STAT, Notch and Wnt/β-catenin signaling pathways may play pivotal roles in this HBV-driven HCC via several circRNAs. Moreover, in non-HBV HCC patients or HCC patients partially infected by HBV, numerous circRNAs have been identified to be important regulators impacting the malignant biological behavior of HCC. Furthermore, the role of circRNAs in HCC drug resistance has become a focus of research with the aim of reversing chemoresistance and immune resistance. Herein, we review the molecular biology of circRNAs in HBV-HCC and their potential in therapeutic strategies.

show abstract

STAT3: A key regulator in liver fibrosis

Cited by 112 publications

References 71 publications

Perturbed transcriptional profiles after chronic low dose rate radiation in mice

Perturbed transcriptional profiles after chronic low dose rate radiation in mice

Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates

Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma

Contact Info

Product

Resources

About