IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis

Liso, Arcangelo; Venuto, Santina; Coda, Anna Rita Daniela; Giallongo, Cesarina; Palumbo, Giuseppe A.; Tibullo, Daniele

doi:10.3390/ijms23084358

Cited by 32 publications

(12 citation statements)

References 83 publications

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“…Similarly, IGFBP6 is associated with inflammation. Although the complete role of IGFBP6 is still largely unknown, it has recently been connected to cardiac remodeling and considered a biomarker for atherosclerotic plaques 22,23 …”

Section: Discussionmentioning

confidence: 99%

“…Although the complete role of IGFBP6 is still largely unknown, it has recently been connected to cardiac remodeling and considered a biomarker for atherosclerotic plaques. 22,23 Our assay included markers of systemic inflammation and vascular function. The proteins involved in systemic inflammation, SAA and CRP, showed moderately increased levels in CAD versus nCAD patients.…”

Section: Protein Combinations Stratify Risk Of Cad Patientsmentioning

confidence: 99%

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Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients

Beatty,

Richardson,

Tran

et al. 2023

Clinical Cardiology

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BackgroundChronic uncontrolled hyperglycemia, a precursor to chronic low‐grade inflammation, is a leading cause of coronary artery disease (CAD) due to plaque buildup in type‐1 diabetes (T1D) patients. We evaluated levels of 22 inflammatory markers in cross‐sectional serum samples from 1222 subjects to evaluate their potential as risk factors for CAD in T1D patients.HypothesisCirculating levels of markers of inflammation may be the risk factors for incident CAD.MethodsThe T1D subjects were divided into two groups: those without CAD (n = 1107) and with CAD (n = 115). Serum levels of proteins were assayed using multiplex immunoassays on a Luminex Platform. Differences between the two groups were made by univariate analysis. Multivariate logistic regression was used to ascertain the potential of proteins as risk factors for CAD. Influence of age, duration of diabetes, sex, hypertension, and dyslipidemia was determined in a stepwise manner. Serum levels of 22 proteins were combined into a composite score using Ridge regression for risk‐based stratification.ResultsMean levels of CRP, IGFBP1, IGFBP2, insulin‐like growth factors binding protein‐6 (IGFBP6), MMP1, SAA, sTNFRI, and sTNFRII were elevated in CAD patients (n = 115) compared to T1D patients without CAD (nCAD, n = 1107). After adjusting for age, duration of diabetes, sex, hypertension, and dyslipidemia, higher levels of sTNFRI (odds ratio [OR] = 2.18, 1.1 × 10−3), sTNFRII (OR = 1.52, 1 × 10−2), and IGFBP6 (OR = 3.62, 1.8 × 10−3) were significantly associated with CAD. The composite score based on Ridge regression, was able to stratify CAD patients into low, medium, and high‐risk groups.ConclusionsThe results show activation of the TNF pathway in CAD patients. Evaluating these markers in serum can be a potential tool for identifying high‐risk T1D patients for intensive anti‐inflammatory therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Protein Combinations Stratify Risk Of Cad Patientsmentioning

confidence: 99%

Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients

Beatty,

Richardson,

Tran

et al. 2023

Clinical Cardiology

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“…DUOXA1 is implicated in the maturation/activation of DUOX1 that is, in turn, a NADPH oxidase known to catalyze ROS production and implicated in innate immune defense and antimicrobial function [ 47 ]. IGFBP6 is involved in the immune response, with both pro- and anti-inflammatory roles [ 48 ], and its expression has been reported to be enhanced following an increase in the fiber/starch ratio in cattle diet [ 49 ]. SLURP1 is a nicotinergic peptide known to exert an anti-inflammatory effect in the human intestinal epithelial cells [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…IGFBP6 is involved in the immune response, with both pro- and anti-inflammatory roles [ 48 ], and its expression has been reported to be enhanced following an increase in the fiber/starch ratio in cattle diet [ 49 ]. SLURP1 is a nicotinergic peptide known to exert an anti-inflammatory effect in the human intestinal epithelial cells [ 48 ]. Notably, up-regulation of DUOXA1, DUOX1, IGFBP6 , and SLURP1 has been highlighted also with NOISeq analysis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage

et al. 2023

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Background Green feed diet in ruminants exerts a beneficial effect on rumen metabolism and enhances the content of milk nutraceutical quality. At present, a comprehensive analysis focused on the identification of genes, and therefore, biological processes modulated by the green feed in buffalo rumen has never been reported. We performed RNA-sequencing in the rumen of buffaloes fed a total mixed ration (TMR) + the inclusion of 30% of ryegrass green feed (treated) or TMR (control), and identified differentially expressed genes (DEGs) using EdgeR and NOISeq tools. Results We found 155 DEGs using EdgeR (p-values < 0.05) and 61 DEGs using NOISeq (prob ≥0.8), 30 of which are shared. The rt-qPCR validation suggested a higher reliability of EdgeR results as compared with NOISeq data, in our biological context. Gene Ontology analysis of DEGs identified using EdgeR revealed that green feed modulates biological processes relevant for the rumen physiology and, then, health and well-being of buffaloes, such as lipid metabolism, response to the oxidative stress, immune response, and muscle structure and function. Accordingly, we found: (i) up-regulation of HSD17B13, LOC102410803 (or PSAT1) and HYKK, and down-regulation of CDO1, SELENBP1 and PEMT, encoding factors involved in energy, lipid and amino acid metabolism; (ii) enhanced expression of SIM2 and TRIM14, whose products are implicated in the immune response and defense against infections, and reduced expression of LOC112585166 (or SAAL1), ROR2, SMOC2, and S100A11, encoding pro-inflammatory factors; (iii) up-regulation of NUDT18, DNAJA4 and HSF4, whose products counteract stressful conditions, and down-regulation of LOC102396388 (or UGT1A9) and LOC102413340 (or MRP4/ABCC4), encoding detoxifying factors; (iv) increased expression of KCNK10, CACNG4, and ATP2B4, encoding proteins modulating Ca2+ homeostasis, and reduced expression of the cytoskeleton-related MYH11 and DES. Conclusion Although statistically unpowered, this study suggests that green feed modulates the expression of genes involved in biological processes relevant for rumen functionality and physiology, and thus, for welfare and quality production in Italian Mediterranean dairy buffaloes. These findings, that need to be further confirmed through the validation of additional DEGs, allow to speculate a role of green feed in the production of nutraceutical molecules, whose levels might be enhanced also in milk.

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“…Moreover, many studies have demonstrated the downregulation of IGFBP6 expression in cancer; in contrast, several studies have shown upregulation of IGFBP6 in pancreatic cancer [ 47 ] and adrenocortical cancer [ 48 ]. Recently, it has been reported that IGFBP6 may exert immunological functions [ 49 , 50 ]. IGFBP6 was found to be highly expressed in eosinophils [ 51 ], and it has also been reported that IGFBP6 is associated with allergic asthma [ 52 ] and thymic atrophy [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Prognostic Value and Immune Infiltration of IGFBP Family Members in Glioblastoma

Zhong

Han

et al. 2022

Journal of Healthcare Engineering

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The insulin-like growth factor-binding protein (IGFBP) family is involved in tumorigenesis and the development of multiple cancers. However, little is known about the prognostic value and regulatory mechanisms of IGFBPs in GBM. Oncomine, Gene Expression Profiling Interactive Analysis, PrognoScan, cBioPortal, LinkedOmics, TIMER, and TISIDB were used to analyze the differential expression, prognostic value, genetic alteration, biological function, and immune cell infiltration of IGFBPs in GBM. We observed that IGFBP1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 mRNA expression was significantly upregulated in patients with GBM, whereas IGFBP6 was downregulated; this difference in mRNA expression was statistically insignificant. Subsequent investigations showed that IGFBP4 and IGFBP6 mRNA levels were significantly associated with overall survival in patients with GBM. Functional Gene Ontology Annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that genes coexpressed with IGFBP4 and IGFBP6 were mainly enriched in immune-related pathways. These results were validated using the TIMER and TSMIDB databases. This study demonstrated that the IGFBP family has prognostic value in patients with GBM. IGFBP4 and IGFBP6 are two members of the IGFBP family that had the highest prognostic value; thus, they have the potential to serve as survival predictors and immunotherapeutic targets in GBM.

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IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis

Cited by 32 publications

References 83 publications

Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients

Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients

Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage

Comprehensive Analysis of Prognostic Value and Immune Infiltration of IGFBP Family Members in Glioblastoma

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