Cytochrome P450 is the most important enzyme in the body and involved in the biotransformation of endogenous substances and exogenous chemicals (Dey et al., 1999). In particular, cytochrome P450 1A2 (CYP1A2) is

Under the stressed condition, a complex feedback mechanism of the hypothalamo-pituitary-adrenal (HPA) axis is activated to regulate interactions to stress to maintain homeostasis of the body (Iwasa et al., 2018;Kim, 2019). In particular, the hormones in HPA axis with respect to corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and glucocorticoid reduce the pulsatile secretions of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH)

Background/Aim: The pathological role of vascular endothelial growth factor receptor 2 (VEGFR-2) in chronic liver injury and liver regeneration is not fully understood. This study analysed the role of VEGFR-2 in liver fibrosis and its regeneration process. Materials and Methods: We administered intraperitoneally 50 mg/kg to 300 mg/kg thioacetamide (TAA) to 9-week-old male mice for 17 weeks. We measured levels of VEGFR-2 protein and identified the location of cells that specifically express VEGFR-2. Results: VEGFR-2 is rarely expressed in normal hepatocytes. However, high VEGFR-2 expression in liver sinusoidal endothelial cells was noted in the TAA group. Conversely, the group that experienced regeneration from liver fibrosis showed significantly higher VEGFR-2 expression in the nucleus of hepatocytes compared to the other groups. Conclusion: VEGFR-2 plays a pivotal role in the nucleus of hepatocytes during liver regeneration and VEGFR-2 may be closely related to cell division. Therefore, VEGFR-2 may be a new therapeutic target for liver regeneration.Liver fibrosis is marked by the formation of an abnormally large amount of scar tissue in the liver (1). Liver fibrosis represents the final common route of chronic liver disease, which eventually leads to cirrhosis (2). Chronic liver disease and cirrhosis result in approximately 35,000 deaths yearly in the United States and cirrhosis is the ninth leading cause of death (3). Therefore, it is very important that liver fibrosis does not progress to cirrhosis, an irreversible stage.Angiogenesis, which is the process of new blood vessel growth from existing vessels, is essential for the physiological functioning of tissues (4). Hepatic angiogenesis is closely associated with the progression of fibrosis in chronic liver diseases (5). According to a recent study, hepatic angiogenesis occurs in chronic liver disease, and is characterized by progressive fibrosis (6). Angiogenesis is a dynamic process regulated by the balance between pro-angiogenic and antiangiogenic factors. Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors (4).Hepatocytes play a key role in angiogenesis, and have a close anatomical relationship with endothelial cells that secrete VEGF (7). VEGF regulates blood and lymphatic vessel development and maintains homeostasis (8). VEGF is primarily produced by endothelial cells in response to hypoxia and by stimulation of growth factors such as transforming growth factor, interleukins or platelet derived growth factor (9, 10). The biological function of VEGF is mediated upon binding to type III receptor tyrosine kinase (RTK), VEGF receptor 1 (VEGFR-1, Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4) (11,12). VEGF stimulates angiogenesis by 1473 This article is freely accessible online.

Objective: The quantitative reverse transcription polymerase chain reaction (qPCR) is the most accurate and reliable technique for analysis of gene expression. Endogenous reference genes (RGs) have been used to normalize qPCR data, although their expression may vary in different tissues and experimental conditions. Verification of the stability of RGs in selected samples is a prerequisite for reliable results. Therefore, we attempted to identify the most stable RGs in the hypothalamic–pituitary–gonadal (HPG) axis in sows.Methods: The cycle threshold values of nine commonly used RGs (<i>18S</i>, <i>HPRT1</i>, <i>GAPDH</i>, <i>RPL4</i>, <i>PPIA</i>, <i>B2M</i>, <i>YWHAZ</i>, <i>ACTB</i>, and <i>SDHA</i>) from HPG axis-related tissues in the domestic sows in the different stages of estrus cycle were analyzed using two RG-finding programs, geNorm and Normfinder, to rank the stability of the pool of RGs. In addition, the effect of the most and least stable RGs was examined by normalization of the target gene, gonadotropin-releasing hormone (<i>GnRH</i>), in the hypothalamus.Results: <i>PPIA</i>, <i>HPRT1</i>, and <i>YWHAZ</i> were the most stable RGs in the HPG axis-related tissues in sows regardless of the stages of estrus cycle. In contrast, traditional RGs, including <i>18S</i> and <i>ACTB</i>, were found to be the least stable under these experimental conditions. In particular, in the normalization of <i>GnRH</i> expression in the hypothalamus against several stable RGs, <i>PPIA</i>, <i>HPRT1</i>, and <i>YWHAZ</i>, could generate significant (p<0.05) elevation of <i>GnRH</i> in the preovulatory phase compared to the luteal phase, but the traditional RGs with the least stability (<i>18S</i> and <i>ACTB</i>) did not show a significant difference between groups.Conclusion: These results indicate the importance of verifying RG stability prior to commencing research and may contribute to experimental design in the field of animal reproductive physiology as reference data.

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