IGF2-NR4A2 Signaling Regulates Macrophage Subtypes to Attenuate Liver Cirrhosis

Yao, Lichao; Han, Xue; Yuan, Man; Zhang, Qiuling; Liu, Pingji; Yang, Linlin; Dai, Kai; Jiang, Yingan

doi:10.14218/jcth.2022.00392

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…BMI1 [378], IGF2 [379], PRKCB (protein kinase C beta) [380], CCL5 [381], E2F1 [382], PF4 [111], CYP11B2 [383], WNT3A [384], COMP (cartilage oligomeric matrix protein) [385], DES (desmin) [335], ANGPTL3 [386], CYP3A5 [387], LRP2 [388], PAH (phenylalanine hydroxylase) [389], HMGCS2 [390], AGXT2 [391], FABP1 [392], CUBN (cubilin) [393], DIO1 [394], MIOX (myo-inositol oxygenase) [344], FGF1 [395], CRY1 [396], PPARGC1A [397], CYP2C8 [398], GC (GC vitamin D binding protein) [399], VNN1 [350], NOX4 [400], EPHX2 [401], F11 [402], AQP2 [403], NAT8 [404], CLDN2 [405], EGF (epidermal growth factor) [406], ANGPT1 [174], CLCN5 [407], KL (klotho) [176], DEFB1 [408], ACE2 [409], NR4A1 [410], SLC13A3 [411], CADM1 [412], AZGP1 [367], DPP4 [413], REN (renin) [414], ABCB1 [415], CCR1 [416], MANBA (mannosidase beta) [417], SELP (selectin P) [418], CLDN16 [419], F8 [420], VCAM1 [421], PLD1 [422], SLCO4C1 [423], TINAG (tubulointerstitial nephritis antigen) [424], SULT1C2 [425], PLAT (plasminogen activator, tissue type) [426] and ALB (albumin) [427] can participate in the occurrence and development of chronic kidney disease. IGF2 [428], SCARNA10 [429], IRF7 [430], PRKCB (protein kinase C beta) [431], CCL5 [432], E2F1 [433], PF4 [434], HOXC8 [435], SMPD3 [118], GREM1 [436], WNT3A [437], COMP (cartilage oligomeric matrix protein) [438], FLI1 [439], DES (desmin) [440], BHMT (betaine--homocysteine ...…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal renal function and structure with increase in serum creatinine level with or without reduced urine output. With the incidence of AKI is increasing. However, the molecular mechanisms of AKI have not been elucidated. It is significant to further explore the molecular mechanisms of AKI. We downloaded the GSE139061 next generation sequencing (NGS) dataset from the Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used to screen the differentially expressed genes (DEGs). Then, the enrichment analysis of DEGs in Gene Ontology (GO) function and REACTOME pathways was analyzed by g:Profiler. Next, the protein-protein interaction (PPI) network and modules was constructed and analyzed, and the hub genes were identified. Next, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were built. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Overall, 956 DEGs were identified, including 478 up regulated and 478 down regulated genes. The enrichment functions and pathways of DEGs involve primary metabolic process, small molecule metabolic process, striated muscle contraction and metabolism. Topological analysis of the PPI network and module revealed that hub genes, including PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 and RPL26L1, might be involved in the development of AKI. miRNA-hub gene and TF-hub gene regulatory networks revealed that miRNAs and TFs including hsa-mir-510-3p, hsa-mir-6086 and mir-146a-5p, MAX and PAX2, might be involved in the development of AKI. Various known and newtherapeutic targets were obtained via network analysis. The results of the current investigation might be beneficial for the diagnosis and treatment of AKI.

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Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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“…Matrix metalloproteinases (MMPs) are key enzymes involved in the degradation and deposition of all proteins in the extracellular matrix and play an important role in the process of tissue remodeling and fibrosis. 14 Huang et al 15 suggested that matrix metalloproteinase-7 (MMP-7) was overexpressed in liver biopsy samples and there was a significant difference when comparing the control group (children with no liver diseases) and the liver transplantation group among children with BA. Lertudomphonwanit et al 16 found that MMP-7 is also highly expressed in the sera of patients with BA, through large-scale, quantitative serum proteomics.…”

Section: Mmp-7mentioning

confidence: 99%

Progress in Biomarkers Related to Biliary Atresia

Kong,

Dong,

Chen

et al. 2024

J Clin Transl Hepatol

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Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children’s liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

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“…IGF2 plays an important role in immune homeostasis and inflammatory response caused by antigen presence (42,(82)(83)(84). This growth factor has a direct effect on immune cells such as macrophages, inhibiting the inflammatory response at low doses (42).…”

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confidence: 99%

IGF2-reprogrammed macrophages ameliorate the inflammatory response and protects against the neurodegenerative and neuroinflammatory process in Parkinson`s disease models.

Grunenwald,

Huerta,

Sepulveda

et al. 2024

Preprint

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Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra, which causes motor deficits. The most common histopathological feature of PD is the presence of α-synuclein (α-syn) misfolding protein and neurotoxic accumulations which leads to neuronal loss. Additionally, the inflammatory response arises as a relevant factor engage in modulate the neurodegeneration process in PD. An increase of proinflammatory cytokines in the blood and brain samples has been reported in PD patients. Also, peripheral blood T cells recognized α-syn, triggering a chronic inflammation in the blood and brain tissue in PD. IGF2 signaling has been involved on cellular reprogramming of macrophages to anti-inflammatory phenotype by epigenetic changes. Moreover, recently a decrease of IGF2 levels was reported in blood samples from PD patients. Methods: The inflammatory response was analyzed by flow cytometry, and qPCR in PBMCs from Chilean PD patients and macrophages isolated from α-syn overexpression transgenic mouse (ASO). We evaluated the motor impairment, systemic inflammation, neurodegeneration, α-syn accumulation and microglial activation in ASO mice treated via intravenous with IGF2-reprogrammed macrophages (MIGF2). Results: We showed a significant increase of proinflammatory markers in PBMCs from PD patients. Also, IGF2 prevented the proinflammatory phenotype triggered by exposure to α-syn PFF in murine primary macrophages. Furthermore, MIGF2 treatment significant decrease the motor impairment, systemic inflammation, and reduce neurodegeneration, α-syn accumulation and microglial activation levels in Substancia Nigra brain region during disease progression in ASO mice. Conclusions: PBMCs from Chilean PD patients showed an increase in proinflammatory profile. Additionally, MIGF2 has a neuroprotective effect in-vitro and in-vivo PD model. MIGF2 prevents motor impairment, neurodegeneration, and inflammation in the brain tissue of ASO mice in different stages of disease progression, suggesting its further application as a possible treatment for PD patients.

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IGF2-NR4A2 Signaling Regulates Macrophage Subtypes to Attenuate Liver Cirrhosis

Abstract: Background and Aims: Liver cirrhosis can lead to liver failure and eventually death. Macrophages are the main contrib-

Cited by 4 publications

References 40 publications

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Progress in Biomarkers Related to Biliary Atresia

IGF2-reprogrammed macrophages ameliorate the inflammatory response and protects against the neurodegenerative and neuroinflammatory process in Parkinson`s disease models.

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