Marked induction of hepatocyte growth factor mRNA in intact kidney and spleen in response to injury of distant organs

doi:10.1016/0006-291X(92)90844-B

Biochemical and Biophysical Research Communications

Volume 186, Issue 2, 31 July 1992, Pages 991-998

https://doi.org/10.1016/0006-291X(92)90844-B Get rights and content

Abstract

Hepatocyte growth factor (HGF) is a potent mitogen for various epithelial cells, including mature hepatocytes and renal tubular cells. Here, HGF mRNA was found to be markedly increased in non-injured kidney and spleen, when the liver or kidney in rats was injured by 70% partial hepatectomy or unilateral nephrectomy. HGF mRNA increased to 3–4 fold higher level than the normal in the kidney and spleen as well as in the remnant liver after partial hepatectomy. Similarly, HGF mRNA markedly increased in the spleen as well as in the remnant kidney after unilateral nephrectomy. These results suggest that the onset of injury to the liver or kidney may be recognized by distal non-injured organs by the signalling of a humoral factor and that HGF derived from these organs may be involved in the regeneration of liver or kidney, through an endocrine mechanism.

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Future investigations into the roles of other known mammalian injury mediators will also further our understanding of progenitor activation mechanisms between species. With clues from mammals (reviewed in (Werner and Grose, 2003)), important candidates to consider include: hepatocyte growth factor (Czaja et al., 1989; Lindroos et al., 1991; Nagaike et al., 1991; Yanagita et al., 1992; Kono et al., 1992; Rodgers et al., 2017), TNF-α (Czaja et al., 1989; Sternbergh et al., 1994; Voss et al., 2017; Ning et al., 2016), IL-1β (Voss et al., 2017), IL-6 (Voss et al., 2017; Ning et al., 2016; Ranganathan et al., 2013), HMGB1 (Sachdev et al., 2013; Dardenne et al., 2013), and IGF (Tonkin et al., 2015; Schertzer et al., 2007; Haugk et al., 1995), among others. Unbiased approaches toward identifying systemic cellular activation cues in highly-regenerative species should also be pursued.
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In these tissues, stromal cells and other cells of the mesenchymal origin such as endothelial cells, stellate cells, Kupffer cells and mononuclear cells express HGF to a variable extent [34,36–39]. Interestingly, liver injury also elicits HGF mRNA expression in distal organs such as lungs, kidneys and spleen [40,41]. Splenic HGF is also induced following skeletal muscle injury [42].
Hepatocyte growth factor (HGF) signaling via the MET receptor is essential for embryonic development and tissue repair. On the other hand, deregulated MET signaling promotes tumor progression in diverse types of cancers. Even though oncogenic MET signaling remains the major research focus, the HGF–MET axis has also been implicated in diverse aspects of immune cell development and functions. In the presence of other hematopoietic growth factors, HGF promotes the development of erythroid, myeloid and lymphoid lineage cells and thrombocytes. In monocytes and macrophages responding to inflammatory stimuli, induction of autocrine HGF–MET signaling can contribute to tissue repair via stimulating anti-inflammatory cytokine production. HGF–MET signaling can also modulate adaptive immune response by facilitating the migration of Langerhans cells and dendritic cells to draining lymph nodes. However, MET signaling has also been shown to induce tolerogenic dendritic cells in mouse models of graft-versus-host disease and experimental autoimmune encephalomyelitis. HGF–MET axis is also implicated in promoting thymopoiesis and the survival and migration of B lymphocytes. Recent studies have shown that MET signaling induces cardiotropism in activated T lymphocytes. Further understanding of the HGF–MET axis in the immune system would allow its therapeutic manipulation to improve immune cell reconstitution, restore immune homeostasis and to treat immuno-inflammatory diseases.
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However, at least for the intravenous application route, it is likely that rAAV's inability to productively transduce nonparenchymal cells of the liver (Figure 2 and ref. 19) could be one of the contributing factors. Although various organs participate in the pathophysiological production and secretion of HGF,36,37,38,39 its natural activity is restricted to sites of tissue injury.39 This restriction is caused by HGF's dependency on activation by coagulation-associated proteases,39 which in turn are activated only at the sites of tissue injury.40
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Hepatocyte growth factor (HGF), a pleiotropic factor regulating development and wound healing, is secreted as inactive pro-HGF and is converted into active HGF by coagulation serine proteases. HGF receptor overexpression can cause massive venous thrombi, and factor Xa is reported to release soluble HGF from granulocytes. We hypothesized that a hypercoagulable condition, such as disseminated intravascular coagulation (DIC), may increase circulating HGF through active cleavage by coagulation serine proteases.
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Marked induction of hepatocyte growth factor mRNA in intact kidney and spleen in response to injury of distant organs

Abstract

FEBS Lett

Biochem. Biophys. Res. Commun

Biochem. Biophys. Res. Commun

Biochem. Biophys. Res. Commun

Biochem. Biophys. Res. Commun

Exp. Cell Res

Biochem. Biophys. Res. Commun

Biochem. Biophys. Res. Commun

FEBS Lett

Biochem. Biophys. Res. Commun

Cell

Biochem. Biophys. Res. Commun

Biochem. Biophys. Res. Commun

FEBS Lett

J. Biol. Chem

Biochem. Biophys. Res. Commun

Anal. Biochem

Biochem. Biophys. Res. Commun