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Insulin-like growth factor-1 mRNA isoforms and insulin-like growth factor-1 receptor mRNA expression in chronic
Aldona Kasprzak1, Agnieszka Adamek1, Wiesława Przybyszewska1
1Aldona Kasprzak, Wiesława Przybyszewska, Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland.
Aim:
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.
Conclusion:
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.
Insights
Hepatitis C virus (HCV) infection alters insulin-like growth factor (IGF)-1 mRNA isoform expression in the liver. These changes suggest HCV may impact IGF-1 splicing, affecting liver disease progression.
Area of Science:
- Molecular Biology
- Hepatology
- Virology
Background:
- Hepatitis C virus (HCV) infection is a major cause of chronic liver disease.
- Insulin-like growth factor (IGF)-1 plays a role in cell growth and differentiation.
- Alterations in IGF-1 signaling pathways have been implicated in various liver diseases.
Purpose of the Study:
- To investigate the expression levels of different insulin-like growth factor (IGF)-1 mRNA isoforms and IGF-1 receptor (IGF-1R) mRNA in liver tissues from patients with chronic hepatitis C (CH-C).
- To correlate IGF-1 and IGF-1R mRNA expression with histological liver damage and clinical parameters in CH-C patients.
Main Methods:
- Quantitative real-time PCR was used to analyze IGF-1 mRNA isoforms (IGF-1A, IGF-1B, IGF-1C, P1, P2) and IGF-1R mRNA expression in liver biopsy specimens from 34 CH-C patients.
- Expression levels were normalized to reference genes and compared between CH-C patients and controls.
- Correlation analysis was performed between gene expression, histological grading/staging (METAVIR), and clinical data (alpha fetoprotein, HCV RNA, steatosis).
Main Results:
- HCV-infected livers showed significantly higher relative expression of total IGF-1 mRNA and specific isoforms (P1, A, C) compared to controls.
- IGF-1A mRNA isoform expression was predominant in both groups.
- Expression of IGF-1 transcripts correlated significantly with each other and with histological grading (lower expression in G2), and negatively with clinical markers like alpha fetoprotein and HCV RNA.
- IGF-1R mRNA expression positively correlated with liver grading and HCV RNA levels.
Conclusions:
- HCV infection significantly alters the quantitative expression of IGF-1 mRNA isoforms in the liver.
- The observed changes in IGF-1 splicing profiles suggest a potential role for HCV in modulating this pathway.
- These alterations may contribute to the pathogenesis of liver disease in CH-C patients.
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