title: Insulin-like growth factor-1 mRNA isoforms and insulin-like growth factor-1 receptor mRNA expression in chronic hepatitis C.
abstract: OBJECTIVE
  To evaluate the expression of different insulin-like growth factor (IGF)-1 mRNA isoforms and IGF-1 receptor (IGF-1R) mRNA in hepatitis C virus (HCV)-infected livers.
  
  
  METHODS
  Thirty-four liver biopsy specimens from chronic hepatitis C (CH-C) patients were obtained before anti-viral therapy. Inflammatory activity (grading) and advancement of fibrosis (staging) were evaluated using a modified point scale of METAVIR. The samples were analyzed using quantitative real-time PCR technique. From fragments of liver biopsies and control liver that were divided and ground in liquid nitrogen, RNA was isolated using RNeasy Fibrous Tissue Mini Kit according to the manufacturer's instruction. Expression levels of IGF-1 mRNA isoforms (IGF-1A, IGF-1B, IGF-1C, P1, and P2) and IGF-1R mRNA were determined through normalization of copy numbers in samples as related to reference genes: glyceraldehyde-3-phosphate dehydrogenase and hydroxymethylbilane synthase. Results on liver expression of the IGF-1 mRNA isoforms and IGF-1R transcript were compared to histological alterations in liver biopsies and with selected clinical data in the patients. Statistical analysis was performed using Statistica PL v. 9 software.
  
  
  RESULTS
  The study showed differences in quantitative expression of IGF-1 mRNA variants in HCV-infected livers, as compared to the control. Higher relative expression of total IGF-1 mRNA and of IGF-1 mRNAs isoforms (P1, A, and C) in HCV-infected livers as compared to the control were detected. Within both groups, expression of the IGF-1A mRNA isoform significantly prevailed over expressions of B and C isoforms. Expression of P1 mRNA was higher than that of P2 only in CH-C. Very high positive correlations were detected between reciprocal expressions of IGF-1 mRNA isoforms P1 and P2 (r = 0.876). Expression of P1 and P2 mRNA correlated with IGF-1A mRNA (r = 0.891; r = 0.821, respectively), with IGF-1B mRNA (r = 0.854; r = 0.813, respectively), and with IGF-1C mRNA (r = 0.839; r = 0.741, respectively). Expression of IGF-1A mRNA significantly correlated with isoform B and C mRNA (r = 0.956; r = 0.869, respectively), and B with C isoforms (r = 0.868) (P < 0.05 in all cases). Lower expression of IGF-1A and B transcripts was noted in the more advanced liver grading (G2) as compared to G1. Multiple negative correlations were detected between expression of various IGF-1 transcripts and clinical data (e.g., alpha fetoprotein, HCV RNA, steatosis, grading, and staging). Expression of IGF-1R mRNA manifested positive correlation with grading and HCV-RNA.
  
  
  CONCLUSIONS
  Differences in quantitative expression of IGF-1 mRNA isoforms in HCV-infected livers, as compared to the control, suggest that HCV may induce alteration of IGF-1 splicing profile.
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Aldona
authors: A
authors: Kasprzak
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Agnieszka
authors: A
authors: Adamek
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Wiesława
authors: W
authors: Przybyszewska
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Przemysław
authors: P
authors: Pyda
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Jacek
authors: J
authors: Szmeja
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Agnieszka
authors: A
authors: Seraszek-Jaros
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Agata
authors: A
authors: Lanzafame
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Anna
authors: A
authors: Surdacka
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Iwona
authors: I
authors: Mozer-Lisewska
authors: Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
authors: Maria
authors: M
authors: Koczorowska
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D019562:Viral Load; D055815:Young Adult
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Chronic hepatitis C; Insulin-like growth factor-1 mRNA isoforms; Insulin-like growth factor-1 receptor; Quantitative polymerase chain reaction