Kar S, Hasegawa K, Carr B I
Pittsburgh Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania 15260, USA.
J Cell Physiol. 1996 Jul;168(1):141-6. doi: 10.1002/(SICI)1097-4652(199607)168:1<141::AID-JCP17>3.0.CO;2-A.
The primary mitogens such as epidermal growth factor and transforming growth factor-alpha are known to stimulate DNA synthesis in primary cultures of adult rat hepatocytes. Vasoactive intestinal polypeptide (VIP) was found to amplify DNA synthesis induced by the primary mitogens and thus acted as a comitogen. The comitogenic effect of VIP was specific for the culture medium, suggesting that minor components in the medium were required for hepatocytes to fully respond to VIP. Glutamic acid is probably one of these minor components, although other components present in the nutrient-rich medium were also necessary for the full comitogenic effect. Other comitogens such as insulin, vasopressin, and angiotensin II interacted additively with low concentrations of VIP. The comitogenic effect of VIP was also found in hepatocytes cultured from regenerating rat liver after a partial hepatectomy. In the regenerating hepatocyte cultures, VIP can act as a mitogen even in the absence of the primary mitogen EGF. VIP mRNA was found in several organs including brain, intestine, and liver, and its expression was slightly induced in liver 24 h after a partial hepatectomy. These results suggest that VIP can act as a hepatic comitogen and may play a role in liver cell proliferation.
已知诸如表皮生长因子和转化生长因子-α等主要促细胞分裂剂可刺激成年大鼠肝细胞原代培养物中的DNA合成。发现血管活性肠肽（VIP）可增强主要促细胞分裂剂诱导的DNA合成，因此作为一种协同促细胞分裂剂发挥作用。VIP的协同促细胞分裂作用对培养基具有特异性，这表明培养基中的微量成分是肝细胞对VIP充分反应所必需的。谷氨酸可能是这些微量成分之一，尽管富含营养的培养基中存在的其他成分对于完全的协同促细胞分裂作用也是必需的。其他协同促细胞分裂剂如胰岛素、血管加压素和血管紧张素II与低浓度的VIP具有相加作用。在部分肝切除术后从再生大鼠肝脏培养的肝细胞中也发现了VIP的协同促细胞分裂作用。在再生肝细胞培养物中，即使在没有主要促细胞分裂剂表皮生长因子（EGF）的情况下，VIP也可作为促细胞分裂剂发挥作用。在包括脑、肠和肝脏在内的多个器官中发现了VIP mRNA，并且在部分肝切除术后24小时肝脏中其表达略有诱导。这些结果表明，VIP可作为肝脏协同促细胞分裂剂，并可能在肝细胞增殖中发挥作用。
