Asai Keiko, Tamakawa Susumu, Yamamoto Masahiro, Yoshie Masumi, Tokusashi Yoshihiko, Yaginuma Yuji, Kasai Shinichi, Ogawa Katsuhiro
Department of Pathology, Asahikawa Medical College, Midorigaoka, Asahikawa, Japan.
Liver Int. 2006 Jun;26(5):595-603. doi: 10.1111/j.1478-3231.2006.01267.x.
Expression of neurotrophins (NTs) and their receptors is increased during hepatic regeneration, but their role is not well understood.
NTs and their receptors were investigated by RT-PCR and immunostaining in regenerating livers after two-thirds hepatectomy (PH) and in hepatocytes and hepatic stellate cells (HSCs) isolated from regenerating livers in mice. Induction of apoptosis after treatment with NGF and the expression of alpha-smooth muscle actin (SMA), interleukin 6 (IL-6) and hepatocyte growth factor (HGF) were also investigated in regenerating HSCs.
Nerve growth factor (NGF) and p75 NT receptor (p75NTR) mRNA were elevated after PH, while other NTs and NT receptors showed no remarkable change. NGF was detected in regenerating hepatocytes, but not in normal hepatocytes. Regenerating HSCs expressed increased p75NTR and SMA in vivo and showed an activated phenotype and the high expression of HGF and IL-6 in vitro. Enhanced cell death was seen in HSCs, both from normal and regenerating liver, after treatment with NGF.
Although activated HSCs may produce the factors that regulate liver regeneration, the de novo NGF production by regenerating hepatocytes may induce the death of activated HSCs via p75NTR, leading to termination of hepatic regeneration.
神经营养因子（NTs）及其受体在肝再生过程中表达增加，但其作用尚未完全明确。
采用逆转录聚合酶链反应（RT-PCR）和免疫染色法，对三分之二肝切除（PH）后再生肝脏以及从小鼠再生肝脏分离出的肝细胞和肝星状细胞（HSCs）中的NTs及其受体进行研究。同时，研究了在再生HSCs中用神经生长因子（NGF）处理后诱导的细胞凋亡以及α-平滑肌肌动蛋白（SMA）、白细胞介素6（IL-6）和肝细胞生长因子（HGF）的表达情况。
PH后神经生长因子（NGF）和p75神经营养因子受体（p75NTR）mRNA水平升高，而其他NTs及其受体无明显变化。在再生肝细胞中检测到NGF，但正常肝细胞中未检测到。再生HSCs在体内p75NTR和SMA表达增加，呈现活化表型，在体外HGF和IL-6表达上调。用NGF处理后，正常肝脏和再生肝脏来源的HSCs均出现细胞死亡增加。
虽然活化的HSCs可能产生调节肝再生的因子，但再生肝细胞新产生的NGF可能通过p75NTR诱导活化HSCs死亡，从而导致肝再生终止。
