Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury.

Yanagita, Kimihiko; Matsumoto, Kunio; Sekiguchi, Kazuma; Ishibashi, Hiromi; Niho, Yoshiyuki; Nakamura, Toshikazu

doi:10.1016/s0021-9258(19)36912-1

Cited by 231 publications

(23 citation statements)

References 34 publications

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“…Our analysis revealed TGF-␤-induced alterations in mesenchymal-epithelial signaling as a possible contributor to impaired organoid-supporting ability. TGF-␤ downregulated FGF10 in phFBs, as previously described in mouse lung stromal cells (41); TGF-␤ also downregulated HGF and FGF7 in phFBs, which encode mesenchyme-produced factors implicated in adult lung repair (42,49,67,72,73). Supplementation with HGF and FGF7 to organoid cultures containing TGF-␤-pretreated phFBs rescued organoid number and significantly increased organoid size.…”

Section: Discussionsupporting

confidence: 67%

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

Ng-Blichfeldt

Jong

Kortekaas

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Transforming growth factor-β (TGF-β)-induced fibroblast-to-myofibroblast differentiation contributes to remodeling in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, but whether this impacts the ability of fibroblasts to support lung epithelial repair remains little explored. We pretreated human lung fibroblasts [primary (phFB) or MRC5 cells] with recombinant human TGF-β to induce myofibroblast differentiation, then cocultured them with adult mouse lung epithelial cell adhesion molecule-positive cells (EpCAM+) to investigate their capacity to support epithelial organoid formation in vitro. While control phFB and MRC5 lung fibroblasts supported organoid formation of mouse EpCAM+ cells, TGF-β pretreatment of both phFB and MRC5 impaired organoid-supporting ability. We performed RNA sequencing of TGF-β-treated phFB, which revealed altered expression of key Wnt signaling pathway components and Wnt/β-catenin target genes, and modulated expression of secreted factors involved in mesenchymal-epithelial signaling. TGF-β profoundly skewed the transcriptional program induced by the Wnt/β-catenin activator CHIR99021. Supplementing organoid culture media recombinant hepatocyte growth factor or fibroblast growth factor 7 promoted organoid formation when using TGF-β pretreated fibroblasts. In conclusion, TGF-β-induced myofibroblast differentiation results in Wnt/β-catenin pathway skewing and impairs fibroblast ability to support epithelial repair likely through multiple mechanisms, including modulation of secreted growth factors.

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Section: Discussionsupporting

confidence: 67%

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

Ng-Blichfeldt

Jong

Kortekaas

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It is required for normal embryogenesis and development 30 , 31 of several organs including the lung 32 . In adults, HGF is produced following injury of the lung tissue and promotes tissue repair 33 – 36 . HGF promotes lung tissue repair through the inhibition of apoptosis of lung epithelial and endothelial cells, and by counteracting a number of pro-apoptotic and pulmonary fibrosis factors such as TGF-β, IL-1β, IL-8, TNF-α, the basic fibroblastic factor, the insulin-like growth factor, and the platelet-derived growth factor 37 – 46 .…”

Section: Discussionmentioning

confidence: 99%

The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients

et al. 2021

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The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a ‘discovery’ cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P < 0.05 to P < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two ‘validation’ cohorts, i.e. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.

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“…4). The expr-essioni of' oiI of vascular HGF is showin to increase in various tissuc inljurics sucIh as i )f blood vessel the liver (Tsuboucihi et a/., 1993: Kawakami et a/., 1994), muscle (Jennisehce el at., 1993), lung (Yanagita et a/., 1993), nfection cause pancreas (Ueda et a/., 1996), and stomach (Talia el at., 1996), issue must be and HGF is believed to be iivolved in the riegencration ot' hc regeneration tissues after inflammation. in dental pulp, The promoter region of' the humilaL IIGF gene has beeni filtrated cells, characterized, and somc sequcinces in the regioll are idenititied nduce HGF by as a conserved sequcnce amonig several acutIC-e phase gencs.…”

Section: Content Of Hgf In Normal and Inflamed Human Dental Pulpsmentioning

confidence: 99%

“…These pleiotropic actions of HGF are mediated via a single receptor, the product of the c-met protooncogene (Bottaro et al, 1991;Naldini et al, 1991). Thus, HGF is now known to be a broad-spectrum and multifunctional cytokine that mediates epithelialand endothelial-mesenchyme interactions (for review, see Goldberg and Rosen, 1993), and is thought to be involved in the regeneration of tissues, such as the liver, after injury and inflammation (Kono et al, 1992;Yanagita et al, 1993;Kawakami et al, 1994;Nakamura et al, 1996;Ueda et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 Predominantly Induces Production of Hepatocyte Growth Factor/Scatter Factor in Human Dental Pulp in Acute Inflammation

Ohnishi¹,

Suwa

Oyama

et al. 2000

J Dent Res

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Hepatocyte growth factor (HGF), which is also known as the scatter factor, is a broad-spectrum and multifunctional cytokine, mediates epithelial-mesenchyme interaction, and is shown to be involved in the development and regeneration of various tissues, including tooth. Here, we report that HGF was present in adult human dental pulps, and its levels increased during acute inflammation of the tissue. Levels of HGF mRNA in dental pulps also increased with inflammation, as determined by reverse-transcription/polymerase chain-reaction. The production of HGF in fibroblasts from dental pulps in culture was dose-dependently stimulated by inflammatory cytokines such as interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha, and by prostaglandin (PG) E2, as determined by an enzyme-linked immunosorbent assay. We also showed that indomethacin did not affect the increase in HGF production by the cells with IL-1alpha, TNF-alpha, and PGE2. The levels of HGF mRNA in the cells were simultaneously increased by these stimulants, as determined by Northern blotting. Since the production of PGs is known to increase at the beginning of inflammation, PGE2 may be involved in the regeneration of dental pulps by the induction of HGF expression after inflammation.

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Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury.

Cited by 231 publications

References 34 publications

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation

The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients

Prostaglandin E2 Predominantly Induces Production of Hepatocyte Growth Factor/Scatter Factor in Human Dental Pulp in Acute Inflammation

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