Mouse endocrine gland-derived vascular endothelial growth factor: a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ-specific angiogenesis.
LeCouter Jennifer,Lin Rui,Frantz Gretchen,Zhang Zemin,Hillan Kenneth,Ferrara Napoleone
We recently described human endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as an endothelial cell mitogen with a novel selective activity and an expression pattern essentially limited to steroidogenic glands. Herein we present the identification and characterization of the mouse ortholog. The mouse cDNA and predicted amino acid sequences are, respectively, 86% and 88% identical with the human. Surprisingly, the mouse EG-VEGF transcript is predominantly expressed in liver and kidney. A comparison of human and mouse EG-VEGF promoter sequences revealed a potential binding site for NR5A1, which is known to be a pivotal element for steroidogenic-specific transcription, in the human but not mouse promoter. In situ hybridization studies localized expression of mouse EG-VEGF mRNA to hepatocytes and renal tubule cells. Interestingly, capillary endothelial cells in these sites share several common structural features with those found in steroidogenic glands. Within liver and kidney, EG-VEGF receptor expression was largely restricted to endothelial cells. Mouse EG-VEGF promoted proliferation and survival of endothelial cells. We propose that mouse EG-VEGF, like human EG-VEGF, plays a role in regulating the phenotype and growth properties of endothelial cells within distinct capillary beds.
Relationship between PK2 and number of Kupffer cells during the progression of liver fibrosis in patients with HBV
Liu Xiao-Qin,Wei Rong-Rong,Wang Cheng-Cheng,Chen Li-Yu,Liu Cong,Liu Kai
Turkish journal of medical sciences
Background/aim: This study aimed to investigate the potential regulatory role of prokineticin 2 (PK2) in modulation of the number and function of Kupffer cells (KCs) during the progression of liver fibrosis in patients with hepatitis B virus (HBV). Materials and methods: We obtained liver tissue sections from 200 patients with HBV undergoing surgical resection in our hospital between January 2013 and July 2016. Of these 200 tissue sections, 150 were fibrosis tissues and 50 were hepatocellular carcinoma tissues. Immunohistochemical evaluations were performed to assess the expression levels of CD68 and PK2 in the sections. The clinical parameters of these 200 patients were also analyzed. Results: As a potential cytokine, PK2 was commonly expressed in KCs. In addition, a close correlation between PK2 and the number of KCs during the progression of liver fibrosis in patients with HBV was found in this study. Conclusion: PK2 is expressed in KCs and participates in the progression of liver fibrosis after HBV infection. As a potential cytokine, PK2 modulates the number of KCs during fibrosis. Thus, PK2 most likely adjusts the number of M1 cells to modulate the role of KCs in the progression of liver fibrosis after HBV infection.
Prokineticin 2 expression as a novel prognostic biomarker for human colorectal cancer.
Yoshida Yu,Goi Takanori,Kurebayashi Hidetaka,Morikawa Mitsuhiro,Hirono Yasuo,Katayama Kanji
Molecular tumor biomarkers hold considerable promise for accurately predicting colorectal cancer (CRC) recurrence and progression. Prokineticin 2 (PROK2) may be associated with angiogenesis and tumor formation in some malignant tumors. However, its prognostic value remains unknown. We focused on the association between PROK2 expression and clinical characteristics of CRC to assess value of PROK2 as a potential biomarker for stage I-III CRC patients prognosis. Between 1992 and 2006, 436 consecutive patients with stage I-III CRC treated with curative resection were included. PROK2 expression in primary tumors was investigated using immunohistochemistry. An animal model of liver metastasis was used to assess the role of PROK2. Positive PROK2 expression in primary tumors was found in 222 of 436 (50.9%) human CRC specimens and was significantly associated with lymphatic invasion, lymph node metastasis, clinical stage, and postoperative liver recurrence rate. Recurrence-free survival was significantly shorter in patients with positive PROK2 expression than in those with negative PROK2 expression. PROK2 expression was an independent unfavorable prognostic indicator for CRC [hazards ratio, 2.119; 95% confidence interval, 1.315-3.415; p = 0.002]. PROK2 overexpression promoted liver metastasis . We suggest that positive PROK2 expression is observed in CRC primary tissues; thus, PROK2 may be a useful predictor for liver recurrence and prognosis in CRC.
Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice.
Jiang Lu,Chu Huikuan,Gao Bei,Lang Sonja,Wang Yanhan,Duan Yi,Schnabl Bernd
Digestive diseases and sciences
BACKGROUND:Alcohol-associated liver disease accounts for half of cirrhosis-related deaths worldwide. The spectrum of disease varies from simple steatosis to fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Understanding the disease on a molecular level helps us to develop therapeutic targets. AIM:We performed transcriptomic analysis in liver and ileum from chronic plus binge ethanol-fed mice, and we assessed the role of selected differentially expressed genes and their association with serum bile acids and gut microbiota. METHODS:Wild-type mice were subjected to a chronic Lieber-DeCarli diet model for 8 weeks followed by one binge of ethanol. RNA-seq analysis was performed on liver and ileum samples. Associations between selected differentially regulated genes and serum bile acid profile or fecal bacterial profiling (16S rDNA sequencing) were investigated. RESULTS:We provide a comprehensive transcriptomic analysis to identify differentially expressed genes, KEGG pathways, and gene ontology functions in liver and ileum from chronic plus binge ethanol-fed mice. In liver, we identified solute carrier organic anion transporter family, member 1a1 (Slco1a1; encoding for organic anion transporting polypeptides (OATP) 1A1), as the most down-regulated mRNA, and it is negatively correlated with serum cholic acid level. Prokineticin 2 (Prok2) mRNA, a cytokine-like molecule associated with gastrointestinal tract inflammation, was significantly down-regulated in ethanol-fed mice. Prok2 mRNA expression was negatively correlated with abundance of Allobaculum (genus), Coprococcus (genus), Lachnospiraceae (family), Lactococcus (genus), and Cobriobacteriaceae (family), while it positively correlated with Bacteroides (genus). CONCLUSIONS:RNA-seq analysis revealed unique transcriptomic signatures in the liver and intestine following chronic plus binge ethanol feeding.