The hepatocyte growth factor (HGF)–MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions

Ilangumaran, Subburaj; Villalobos-Hernandez, Alberto; Bobbala, Diwakar; Ramanathan, Sheela

doi:10.1016/j.cyto.2015.12.013

Cited by 67 publications

(58 citation statements)

References 196 publications

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“…These findings suggest that BM-A do not specifically exert an inhibitory effect on hematopoiesis itself, but rather that they presence in the culture supernatant suggests that BM-A can play both roles to meet the homeostatic requirements of the BM niche (Ilangumaran, Villalobos-Hernandez, Bobbala, & Ramanathan, 2016).…”

Section: Bm-amentioning

confidence: 88%

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Bone marrow adipocytes support hematopoietic stem cell survival

Mattiucci

Maurizi

Izzi

et al. 2017

Journal Cellular Physiology

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In bone marrow (BM), hematopoietic elements are mingled with adipocytes (BM-A), which are the most abundant stromal component in the niche. BM-A progressively increase with aging, eventually occupying up to 50% of BM cavities. In this work, the role played by BM-A was explored by studying primary human BM-A isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human hematopoietic stem cells (HSC) by the long-term culture initiating cell (LTC-IC) assay. Findings demonstrated that BM-A are capable of supporting HSC survival in the LTC-IC assay, since after 5 weeks of co-culture, HSC were still able to proliferate and differentiate. Furthermore, critical molecules such as C-X-C motif chemokine 12 (CXCL12), interleukin (IL)-8, colony-stimulating factor 3 (CSF3), and leukaemia inhibitory factor (LIF), were expressed at similar levels in BM-A and in primary human BM mesenchymal stromal cells (BM-MSC), whereas IL-3 was higher in BM-A. Interestingly, BM-A displayed a different gene expression profile compared with subcutaneous adipose tissue adipocytes (AT-A) collected from abdominal surgery patients, especially in terms of regulation of lipid metabolism, stemness genes, and white-to-brown differentiation pathways. Accordingly, analysis of the gene pathways involved in hematopoiesis regulation showed that BM-A are more closely related to BM-MSC than to AT-A. The present data suggest that BM-A play a supporting role in the hematopoietic niche and directly sustain HSC survival.

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Section: Bm-amentioning

confidence: 88%

“…These molecules can both induce HSC quiescence and stimulate their differentiation. Their presence in the culture supernatant suggests that BM‐A can play both roles to meet the homeostatic requirements of the BM niche (Ilangumaran, Villalobos‐Hernandez, Bobbala, & Ramanathan, ).…”

Section: Discussionmentioning

confidence: 99%

Bone marrow adipocytes support hematopoietic stem cell survival

Mattiucci

Maurizi

Izzi

et al. 2017

Journal Cellular Physiology

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“…We also observed that almost all the pro-and anti-inflammatory cytokines increased in HGF-Tg mice, although the differences showed no statistical significance. So HGF can contribute to anti-inflammatory effect and wound repair via adjusting cytokine production [10].…”

Section: Recent Studies Have Described the Indispensable Contributionmentioning

confidence: 99%

“…HGF expression was found to be upregulated following a variety of injuries; it was postulated that cells of the immune system contribute to regulating the expression of HGF and c-Met following injury and inflammation [7,8,9].HGF promotes the development of immune cells and contributes to immune responses and tissue repair [10,11]. Moreover, HGF was reported to inhibit the secretion of inflammatory cytokines and to promote secretion of anti-inflammatory cytokines [12,13].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effect of HGF responses to traumatic oral ulcers using an HGF-Tg mouse model

Wang

Yan

Tang

et al. 2020

Preprint

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Background: Hepatocyte growth factor (HGF) has been implicated in inhibiting diverse types of inflammation and promoting wound healing. In this study, we demonstrate the anti-inflammatory effect of HGF on traumatic ulcer of oral mucosa using HGF overexpression transgenic C57BL/6 (HGF-Tg) mice. In total, 29 C57BL/6 (WT) and 29 HGF-Tg mice were used in this study. Traumatic ulcer of left mucosa was performed by abrasion using a n 15 surgery knife. Ulcer tissues and serum samples were collected on 5 th day, histological score, expression of inflammatory cells and serum cytokines expression were measured and analyzed. Results: There existed statistical significant difference in connective Ly6G positive cells and NF-кB positive expression, HGF-Tg mice showed lower number of positive cells ( p =0.048, p =0.020 ). Eotaxin ( t -test, p =0.002), MIP-1gamma ( t -test, p =0.011), BLC ( t -test, p =0.03),Eotaxin-2 ( t -test, p =0.027), RANTES ( t -test, p =0.038), Lix ( t -test, p =0.04) and IL-3 ( t -test, p =0.047) had statistical significance higher expression in HGF-Tg mice. No significant difference of blood T cells ( p =0.998), Neutrophils ( p =0.331),Macrophages ( p =0.470) and CD4+/CD8+ ratio ( p =0.451) between HGF-Tg and WT group. Conclusions: We observed that HGF-Tg animals presented less Ly6G-positive neutrophil infiltration, higher levels of circulating cytokines and less NF- к B expression in connective tissue, with a positive effect on the healing of oral traumatic ulcers. Key words: HGF, oral ulcer, cytokine, inflammation

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“…From a functional perspective, how might MET signaling be involved? Within the immune system, MET expression is low in inactive cells, but increases following activation in several cell classes, including monocytes/macrophages, dendritic cells and B cells (24, 83, 84). Normally, MET negatively regulates immune responsiveness in mice, attenuating inflammatory responses in a variety of contexts (85, 86).…”

Section: Met the Periphery And Asd: Gi And Immune Functionsmentioning

confidence: 99%

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism

Eagleson

Levitt

2017

Biological Psychiatry

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People with autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy - the influence of one gene on distinct phenotypes - raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multi-functional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain, and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with ASD, reduces transcription and disrupts socially-relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways, and has a complex protein interactome that is enriched in ASD and other NDD candidates. The interactome is co-regulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, impacting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms.

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The hepatocyte growth factor (HGF)–MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions

Cited by 67 publications

References 196 publications

Bone marrow adipocytes support hematopoietic stem cell survival

Bone marrow adipocytes support hematopoietic stem cell survival

Anti-inflammatory effect of HGF responses to traumatic oral ulcers using an HGF-Tg mouse model

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism

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