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Liver sinusoidal endothelial cells (LSEC) control organ functions, metabolism, and development through the secretion of angiokines. LSEC express hepatocyte growth factor (Hgf), which is involved in prenatal development, metabolic homeostasis, and liver regeneration. This study aimed to elucidate the precise contribution of LSEC-derived Hgf in physiologic homeostasis and liver regeneration. Stab2-iCre;Hgf (Hgf) mice were generated to abrogate Hgf expression selectively in LSEC from early fetal development onwards, to study global development, metabolic and endothelial zonation, and organ functions as well as liver regeneration in response to 70% partial hepatectomy (PH). Although zonation and liver-to-body weight ratios were not altered, total body weight, and total liver weight were reduced in Hgf. Necrotic organ damage was more marked in Hgf mice and regeneration was delayed 72h after PH. This was associated with decreased hepatocyte proliferation at 48h after PH. Molecularly, Hgf mice showed down-regulation of Hgf/c-MET signaling and decreased expression of Deptor in hepatocytes. In vitro knock-down of Deptor was associated with decreased proliferation. Therefore, angiocrine Hgf controls hepatocyte proliferation and susceptibility to necrosis following partial hepatectomy via the Hgf/c-Met axis involving Deptor to prevent excessive organ damage.
This article was published in the following journal.
Name: The American journal of pathology
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Gradual increase in the number, the size, and the complexity of cells of an individual. Growth generally results in increase in ORGAN WEIGHT; BODY WEIGHT; and BODY HEIGHT.
An analytical technique for measuring particle size of molecules that are less than a micron in diameter dispersed or dissolved in a liquid.
The measurement of an organ in volume, mass, or heaviness.
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Systematic study of the body and the use of its static and dynamic position as a means of communication.
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