Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach

Jangphattananont, Nawaphat; Sato, Hiroki; Imamura, Ryu; Sakai, Katsuya; Terakado, Yumi; Murakami, Kazuhiro; Barker, Nick; Oshima, Hiroko; Oshima, Masanobu; Takagi, Junichi; Kato, Yukinari; Yano, Seiji; Matsumoto, Kunio

doi:10.3390/ijms20122955

Cited by 13 publications

(11 citation statements)

References 42 publications

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“…In the esophagus, we identified the smooth muscle layer, which serves as a scaffold for myogenic progenitor migration, to be a major source of Hgf . This finding is in agreement with a recent study showing that HGF is mainly localized in smooth muscle cells in endodermal organs including the stomach and esophagus (Jangphattananont et al, 2019). Thus, our data highlight the functional coordination between adjacent but distinct smooth and striated muscle progenitors that facilitate ESM patterning which is unique compared to muscle patterning elsewhere.…”

Section: Discussionsupporting

confidence: 94%

A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

Comai

Heude

Mella

et al. 2019

eLife

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In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.

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Section: Discussionsupporting

confidence: 94%

A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

Comai

Heude

Mella

et al. 2019

eLife

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“…In the stomach, scHGF is mainly expressed and localized in smooth muscle cells, while tcHGF is mainly localized in the epithelial gland base region. Importantly, tcHGF localization nearly overlaps with the localization of activated MET (pMET), and pMET in the glandular base region is closely associated with the localization of gastric epithelial stem cells, again indicating the importance of tcHGF in MET activation [15].…”

Section: Introductionmentioning

confidence: 87%

“…activated MET (pMET), and pMET in the glandular base region is closely associated with the localization of gastric epithelial stem cells, again indicating the importance of tcHGF in MET activation [15].…”

Section: Discovery and Specificitymentioning

confidence: 96%

“…In normal tissues, HGF mainly exists as scHGF, while the processing of scHGF into tcHGF occurs in injured tissues [14], indicating that the local processing of scHGF to tcHGF may play an important role in regulating MET receptor activation following a tissue injury. Although the localization of tcHGF and scHGF had not been elucidated, the distinct localization of tcHGF from scHGF was demonstrated recently, using a tcHGF-specific antibody [15]. In the stomach, scHGF is mainly expressed and localized in smooth muscle cells, while tcHGF is mainly localized in the epithelial gland base region.…”

Section: Introductionmentioning

confidence: 99%

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Cyclic Peptide-Based Biologics Regulating HGF-MET

Sato

Imamura

Suga

et al. 2020

IJMS

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Using a random non-standard peptide integrated discovery system, we obtained cyclic peptides that bind to hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor. (MET) HGF-inhibitory peptide-8 (HiP-8) selectively bound to two-chain active HGF, but not to single-chain precursor HGF. HGF showed a dynamic change in its molecular shape in atomic force microscopy, but HiP-8 inhibited dynamic change in the molecular shape into a static status. The inhibition of the molecular dynamics of HGF by HiP-8 was associated with the loss of the ability to bind MET. HiP-8 could selectively detect active HGF in cancer tissues, and active HGF probed by HiP-8 showed co-localization with activated MET. Using HiP-8, cancer tissues with active HGF could be detected by positron emission tomography. HiP-8 seems to be applicable for the diagnosis and treatment of cancers. In contrast, based on the receptor dimerization as an essential process for activation, the cross-linking of the cyclic peptides that bind to the extracellular region of MET successfully generated an artificial ligand to MET. The synthetic MET agonists activated MET and exhibited biological activities which were indistinguishable from the effects of HGF. MET agonists composed of cyclic peptides can be manufactured by chemical synthesis but not recombinant protein expression, and thus are expected to be new biologics that are applicable to therapeutics and regenerative medicine.

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“…It has been more than three decades since HGF was originally discovered as a hormone-like substance in the serum that was highly mitogenic for hepatocytes (Nakamura et al, 1984;Oliveira et al, 2018). HGF is initially produced and secreted by stromal cells (mainly fibroblasts and smooth muscle cells) in the form of pro-HGF that is biologically inactive (Miyazawa et al, 1994(Miyazawa et al, , 1996Jangphattananont et al, 2019). The single chain Pro-HGF is then proteolytically cleaved at Arg 494 and Val 495 , generating mature HGF in a heterogeneous two-chain form (Miyazawa et al, 1993;Naldini et al, 1995;Kawaguchi and Kataoka, 2014).…”

Section: Structural and Functional Characteristics Of Hgf And C-metmentioning

confidence: 99%

Structural and Functional Insight Into the Glycosylation Impact Upon the HGF/c-Met Signaling Pathway

Tang

Liu

et al. 2020

Front. Cell Dev. Biol.

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Upon interactions with its specific ligand hepatocyte growth factor (HGF), the c-Met signal is relayed to series of downstream pathways, exerting essential biological roles. Dysregulation of the HGF-c-Met signaling pathway has been implicated in the onset, progression and metastasis of various cancers, making the HGF-c-Met axis a promising therapeutic target. Both c-Met and HGF undergo glycosylation, which appears to be biologically relevant to their function and structural integrity. Different types of glycoconjugates in the local cellular environment can also regulate HGF/c-Met signaling by distinct mechanisms. However, detailed knowledge pertaining to the glycosylation machinery of the HGF-c-Met axis as well as its potential applications in oncology research is yet to be established. This mini review highlights the significance of the HGFc-Met signaling pathway in physiological and pathological context, and discusses the molecular mechanisms by which affect the glycosylation of the HGF-c-Met axis. Owing to the crucial role played by glycosylation in the regulation of HGF/c-Met activity, better understanding of this less exploited field may contribute to the development of novel therapeutics targeting glycoepitopes.

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Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach

Cited by 13 publications

References 42 publications

A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

Cyclic Peptide-Based Biologics Regulating HGF-MET

Structural and Functional Insight Into the Glycosylation Impact Upon the HGF/c-Met Signaling Pathway

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