Impaired liver regeneration in acute liver failure: the significance of cross‐communication of growth associated factors in liver regeneration

Abstract

Liver regeneration is considered to be retarded or suppressed in patients with acute liver failure. However, the mechanisms for this suppression remain to be elucidated. In order to evaluate deficiencies in liver regeneration in patients with acute liver failure, we focused on the cross-communication of growth-associated factors in experimental models. In primary cultured rat hepatocytes, the levels of cellular p53 and transforming growth factor-alpha (TGF-alpha), as well as DNA synthesis increased by the addition of hepatocyte growth factor (HGF). When p53 activity was suppressed, TGF-alpha expression and DNA synthesis were reduced. DNA synthesis was also reduced when TGF-alpha activity was suppressed. In rats after partial hepatectomy, hepatic HGF and p53 protein levels increased, followed by an increase of hepatic TGF-alpha levels and hepatocyte proliferation. Circulating levels of HGF and TGF-alpha correlated with changes in the hepatic levels. The suppression of TGF-alpha activity reduced the proliferation of hepatocytes in these rats. In patients suffering from acute hepatitis, serum HGF levels increased followed by an increase of serum TGF-alpha levels. In contrast, in patients with acute liver failure, the increase of serum TGF-alpha levels was suppressed depending on the severity of hepatic failure, even though serum HGF levels markedly increased. The patients' hepatic levels were consistent with serum levels. Cross-communication of growth associated factors may be important in the progression of liver regeneration, and impaired regenerative capacity in patients with acute liver failure may be attributable, at least in part, to a disruption of communication of growth-associated factors.

Characterization and Evaluation of HGF-Loaded PLGA Nanoparticles in a CCl4-Induced Acute Liver Injury Mouse Model

“…The effects are generated through the HGF/MET axis [17,18]. Several studies have confirmed that HGF can promote cell proliferation and migration and inhibit apoptosis and tissue fibrosis [19][20][21].…”

Autocrine-Controlled Formation and Function of Tissue-Like Aggregates by Primary Hepatocytes in Micropatterned Hydrogel Arrays

“…[47][48][49][50] The ability of primary hepatocytes to form tissue-like structures on micromolded PEG-fibrinogen gels in the absence of any of these growth factors provided exogenously implicates autocrine signaling. To examine the presence of autocrine growth factors, primary hepatocytes were cultured in serum-free medium devoid of exogenous growth factors and then fixed and stained with antibodies against EGF, HGF, and TGF-a at days 3, 7, and 10.…”

Effect of Single Intake of Exogenous Hepatocytes Growth Inducer on the Indices of Non-Specific Resistance Under Conditions of Postresection Liver Injury

“…После обширных резекций выделенный клетками в ответ на повреждение фактор роста гепатоцитов способствует регенерации поврежденной печени, активизирует белково-синтетическую функцию печени [19,21,24].…”