Abstract:Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha … Show more
“…Moreover, ANG may have antiinflammatory activity because its protein concentrations in serum are increased during the inflammatory response or tumour necrosis factor alpha and interleukin -1β treatment [102,118,119]. The mechanisms by which ANG suppresses the inflammatory response may involve the inhibition of TBK1-mediated NF-κB nuclear translocation [120]. Additional data are required to support this suggestion.…”
Section: Ang Participates In Immune Responsesmentioning
As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was first isolated and identified solely by its ability to induce new blood vessel formation, and now, it has been recognized to play important roles in various physiological and pathological processes through regulating cell proliferation, survival, migration, invasion, and/or differentiation. ANG exhibits very weak ribonucleolytic activity that is critical for its biological functions, and exerts its functions through activating different signaling transduction pathways in different target cells. A series of recent studies have indicated that ANG contributes to cellular nucleic acid metabolism. Here, we comprehensively review the results of studies regarding the structure, mechanism, and function of ANG over the past three decades. Moreover, current problems and future research directions of ANG are discussed. The understanding of the function and mechanism of ANG in a wide context will help to better delineate its roles in diseases, especially in cancer and neurodegenerative diseases.
“…Moreover, ANG may have antiinflammatory activity because its protein concentrations in serum are increased during the inflammatory response or tumour necrosis factor alpha and interleukin -1β treatment [102,118,119]. The mechanisms by which ANG suppresses the inflammatory response may involve the inhibition of TBK1-mediated NF-κB nuclear translocation [120]. Additional data are required to support this suggestion.…”
Section: Ang Participates In Immune Responsesmentioning
As a member of the vertebrate-specific secreted ribonucleases, angiogenin (ANG) was first isolated and identified solely by its ability to induce new blood vessel formation, and now, it has been recognized to play important roles in various physiological and pathological processes through regulating cell proliferation, survival, migration, invasion, and/or differentiation. ANG exhibits very weak ribonucleolytic activity that is critical for its biological functions, and exerts its functions through activating different signaling transduction pathways in different target cells. A series of recent studies have indicated that ANG contributes to cellular nucleic acid metabolism. Here, we comprehensively review the results of studies regarding the structure, mechanism, and function of ANG over the past three decades. Moreover, current problems and future research directions of ANG are discussed. The understanding of the function and mechanism of ANG in a wide context will help to better delineate its roles in diseases, especially in cancer and neurodegenerative diseases.
“…; Lee et al . ). In contrast to these two growth factors, FGF‐2 is not typically associated with liver repair, and genetic deletion does not impair regeneration after PHx (Sturm et al .…”
Section: Resultsmentioning
confidence: 97%
“…HGF is a potent mitogen and strongly contributes to hepatocyte entry into the cell cycle (Taub, 2004;Michalopoulos, 2007). Ang-1 contributes to regulation of angiogenesis in a variety of pathological conditions and has been shown to be involved in several processes involved in liver recovery from hepatectomy, including wound healing and negative regulation of inflammation (Pan et al 2012;Lee et al 2014). In contrast to these two growth factors, FGF-2 is not typically associated with liver repair, and genetic deletion does not impair regeneration after PHx (Sturm et al 2004).…”
Section: Biochemical Analysis Revealed An Altered Balance Of Cytokinementioning
Key pointsr Loss of adiponectin delays the initiation of liver regeneration after partial hepatectomy, but later accelerates regeneration.r Loss of adiponectin modulates these regeneration kinetics through decreased hepatocyte response to inflammation and increased growth factor bioavailability.r Increased adiponectin suppresses liver regeneration through decreased growth factor bioavailability.r Our predictive computational model was able to connect these molecular regulatory events to tissue physiology.Abstract Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn -/-mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn -/-mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. Abbreviations Adn, adiponectin; Adn -/-, adiponectin knockout; Ang-1, angiogenin-1; β, response parameter; CCl 4 , carbon tetrachloride; DLS, dynamic local sensitivity; ECM, extracellular matrix; FGF-2 or bFGF, fibroblast growth factor 2; GF, growth factor; HGF, hepatocyte growth factor; IE, immediate early; IL-6, interleukin 6; JAK, Janus kinase; k i SOCS3 , SOCS3 inhibition parameter of STAT3 production; k M XX , Michaelis-Menten constant; k prol , replication rate; k P , P to R rate parameter; k Q , Q to P rate parameter; k R , R to Q rate parameter; k up , GF uptake rate by ECM; k XX , XX production rate; k 1 -k 7 , steady-state molecular production rates; κ XX , XX degradation rate; M, metabolic demand; M/N, metabolic load; N, number of hepatocytes; P, primed; PBS, phase-based sensitivity; PHx, partial hepatectomy; PS, pulsatile sensitivity; PSA, pulsatile sensitivity analysis; pSTAT3, phosphorylated STAT3; proSTAT3, monomeric STAT3; θ, threshold parameter; Q, quiescent; R, replicating; SHP-1, Src homology region 2 domain-containing...
“…STAT3 controls inhibitor of kappa light polypeptide gene enhancer in B cells, kinase epsilon (IKBKE) production 16 . Additionally, TANK binding kinase 1 (TBK1) and IKBKE, two members of the IκB kinase family, mediate the inflammatory response 17, 18 . Based on these findings, Ssu72 may regulate the inflammatory response by binding to STAT3.Figure 2Ssu72 controls inflammatory responses in vitro .…”
Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro. A systemic infusion of Ssu72 attenuates experimental autoimmune arthritis by reducing STAT3 activity and the differentiation of Th17 cells. It also reduces joint destruction, serum immunoglobulin concentrations and osteoclastogenesis but increases the number of marginal zone B cells and B10 cells. These effects are associated with reduced p-STAT3 levels and the suppression of Th17 cell formation in vivo. Based on these data, Ssu72 is related to STAT3 activation and the inflammatory response; and Ssu72 overexpression in T-cell-mediated immunity has potential utility for the treatment of autoimmune arthritis.
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