IGFBP-5 Promotes Fibrosis via Increasing Its Own Expression and That of Other Pro-fibrotic Mediators

Nguyen, Xinh Xinh; Muhammad, Lutfiyya N.; Nietert, Paul J.; Feghali‐Bostwick, Carol

doi:10.3389/fendo.2018.00601

Cited by 58 publications

(62 citation statements)

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“…Findings with IGFBP2 are consistent with our previous studies showing increased expression of IGFBP3 and IGFBP5 in IPF and SSc-PF (25,26) and reinforced the crucial role that IGFBPs and the IGF pathway play in the development and perpetuation of pulmonary fibrosis (22)(23)(24). Note however that IGFBPs can also signal via membrane bound proteins such as integrins in a IGF-independent pathway (59).…”

Section: Targeting Igfbp2 and Igfl2supporting

confidence: 90%

“…We and others have previously shown that the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are key players in the development and progression of pulmonary fibrosis (22)(23)(24)(25)(26)(27). IGFBP3, IGFBP5, and IGFBP7 have been previously shown to be upregulated in both lung tissues and lung fibroblasts from patients with SSc-PF and IPF (24)(25)(26). IGFBP4 is downregulated in SSc lung fibroblasts (27), and upregulated in IPF lung tissues (28,29).…”

Section: Upregulation Of Igfbp2 and Igfl2 Is Common To Both Diseasesmentioning

confidence: 99%

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Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis

et al. 2020

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Scleroderma-associated pulmonary fibrosis (SSc-PF) and idiopathic pulmonary fibrosis (IPF) are two of many chronic fibroproliferative diseases that are responsible for nearly 45% of all deaths in developed countries. While sharing several pathobiological characteristics, they also have very distinct features. Currently no effective anti-fibrotic treatments exist that can halt the progression of PF or reverse it. Our goal is to uncover potential gene targets for the development of anti-fibrotic therapies efficacious in both diseases, and those specific to SSc-PF, by identifying universal pathways and molecules driving fibrosis in SSc-PF and IPF tissues as well as those unique to SSc-PF. Using DNA microarray data, a meta-analysis of the differentially expressed (DE) genes in SSc-PF and IPF lung tissues (diseased vs. normal) was performed followed by a full systems level analysis of the common and unique transcriptomic signatures obtained. Protein-protein interaction networks were generated to identify hub proteins and explore the data using the centrality principle. Our results suggest that therapeutic strategies targeting IL6 trans-signaling, IGFBP2, IGFL2, and the coagulation cascade may be efficacious in both SSc-PF and IPF. Further, our data suggest that the expression of matrikine-producing collagens is also perturbed in PF. Lastly, an overall perturbation of bioenergetics, specifically between glycolysis and fatty acid metabolism, was uncovered in SSc-PF. Our findings provide insights into potential targets for the development of anti-fibrotic therapies that could be effective in both IPF and SSc-PF.

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Section: Targeting Igfbp2 and Igfl2supporting

confidence: 90%

Section: Upregulation Of Igfbp2 and Igfl2 Is Common To Both Diseasesmentioning

confidence: 99%

Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis

et al. 2020

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“…Exogenous and endogenously expressed IGFBP-5 was found to increase the expression of ECM component genes and pro-fibrotic genes in primary human IPF fibroblasts in vitro (150). IGFBP-5 was also shown to increase expression of its own gene in these cells, leading to a positive feedback loop that may play a role in IPF pathogenesis (150).…”

Section: Igfbp-5 In Pathology and Disease Statesmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein-5 in Physiology and Disease

Duan

Allard

2020

Front. Endocrinol.

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Insulin-like growth factor (IGF) signaling is regulated by a conserved family of IGF binding proteins (IGFBPs) in vertebrates. Among the six distinct types of IGFBPs, IGFBP-5 is the most highly conserved across species and has the broadest range of biological activities. IGFBP-5 is expressed in diverse cell types, and its expression level is regulated by a variety of signaling pathways in different contexts. IGFBP-5 can exert a range of biological actions including prolonging the half-life of IGFs in the circulation, inhibition of IGF signaling by competing with the IGF-1 receptor for ligand binding, concentrating IGFs in certain cells and tissues, and potentiation of IGF signaling by delivery of IGFs to the IGF-1 receptor. IGFBP-5 also has IGF-independent activities and is even detected in the nucleus. Its broad biological activities make IGFBP-5 an excellent representative for understanding IGFBP functions. Despite its evolutionary conservation and numerous biological activities, knockout of IGFBP-5 in mice produced only a negligible phenotype. Recent research has begun to explain this paradox by demonstrating cell type-specific and physiological/pathological context-dependent roles for IGFBP-5. In this review, we survey and discuss what is currently known about IGFBP-5 in normal physiology and human disease. Based on recent in vivo genetic evidence, we suggest that IGFBP-5 is a multifunctional protein with the ability to act as a molecular switch to conditionally regulate IGF signaling.

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“…IGFBP-5 binds to endothelial cell monolayers by its cysteine residues [20] and could act in tissue remodeling. It also stimulates collagen production and upregulates extracellular matrix genes [21] and is reported to inhibit phosphorylation of ERK1/2, and p38-MAPK kinases. [22] EFEMP1 encodes glycoproteins composing the extracellular matrix component.…”

Section: Plos Onementioning

confidence: 99%

Regulatory effects of Lactobacillus plantarum HY7714 on skin health by improving intestinal condition

et al. 2020

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Despite increasing research on the gut-skin axis, there is a lack of comprehensive studies on the improvement of skin health through the regulation of the intestinal condition in humans. In this study, we investigated the benefits of Lactobacillus plantarum HY7714 (HY7714) consumption on skin health through its modulatory effects on the intestine and ensuing immune responses. HY7714 consumption led to differences in bacterial abundances from phylum to genus level, including increases in Actinobacteria followed by Bifidobacterium and a decrease in Proteobacteria. Additionally, HY7714 significantly ameliorated inflammation by reducing matrix metallopeptidases (MMP-2 and MMP-9), zonulin, and calprotectin in plasma, all of which are related to skin and intestinal permeability. Furthermore, RNA-seq analysis revealed its efficacy at restoring the integrity of the gut barrier by regulating gene expression associated with the extracellular matrix and immunity. This was evident by the upregulation of IGFBP5, SERPINE1, EFEMP1, COL6A3, and SEMA3B and downregulation of MT2A, MT1E, MT1X, MT1G, and MT1F between TNFα and TNFα plus HY7714 treated Caco-2 cells. These results propose the potential mechanistic role of HY7714 on skin health by the regulation of the gut condition. OPEN ACCESS Citation: Nam B, Kim SA, Park SD, Kim HJ, Kim JS, Bae CH, et al. (2020) Regulatory effects of Lactobacillus plantarum HY7714 on skin health by improving intestinal condition. PLoS ONE 15(4): e0231268. https://doi.org/10.

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IGFBP-5 Promotes Fibrosis via Increasing Its Own Expression and That of Other Pro-fibrotic Mediators

Cited by 58 publications

References 50 publications

Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis

Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis

Insulin-Like Growth Factor Binding Protein-5 in Physiology and Disease

Regulatory effects of Lactobacillus plantarum HY7714 on skin health by improving intestinal condition

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