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Published on: July 15, 2021
The effects of TRPM2, TRPM6, TRPM7 and TRPM8 gene expression in hepatic ischemia reperfusion injury
T Bilecik1, F Karateke, H Elkan
1Department of Surgery, Istinye University, Faculty of Medicine, VM Mersin Medical Park Hospital, Mersin, Turkey. karatekefaruk@gmail.com.
Objective:
Mammalian transient receptor potential melastatin (TRPM) channels are a form of calcium channels and they transport calcium and magnesium ions. TRPM has eight subclasses including TRPM1-8. TRPM2, TRPM6, TRPM7, TRPM8 are expressed especially in the liver cell. Therefore, we aim to investigate the effects of TRPM2, TRPM6, TRPM7, and TRPM8 gene expression and histopathologic changes after treatment of verapamil in the hepatic ischemia-reperfusion rat model.
Materials And Methods:
Animals were randomly assigned to one or the other of the following groups including sham (n=8) group, verapamil (calcium entry blocker) (n=8) group, I/R group (n=8) and I/R- verapamil (n=8) group. TRPM 2, 6, 7, 8 gene expression level was were assessed by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and histopathologic changes were determined by the hematoxylin and eosin (HE) examination.
Results:
The expression level of TRPM 2, 6, 7, and 8 genes was were significantly higher in ischemia-reperfusion (I/R), verapamil, IR-verapamil groups compared to sham group. The p-values were 0.0024, < 0.0001, 0.0002, 0.006 for TRPM2, TRPM6, TRPM7, and TRPM8, respectively. Severe necrotic, degenerative differentiations and severe hemorrhagic areas were observed in hepatocytes from IR group. Also, moderate necrotic and degenerative differentiations and moderate hemorrhagic areas were observed in hepatocytes from IR-verapamil group.
Conclusions:
This is the first study reporting an association between the expression level of TRPM 2, 6, 7, 8 in a hepatic ischemia-reperfusion rat model. Moreover, TRPM 2, 6, 7, 8 affect hepatic ischemia-reperfusion.
Insights
This study investigated Transient Receptor Potential Melastatin (TRPM) channels in liver injury. Verapamil treatment affected TRPM gene expression and liver cell damage in a rat model of hepatic ischemia-reperfusion.
Area of Science:
- Physiology
- Molecular Biology
- Pharmacology
Background:
- Transient Receptor Potential Melastatin (TRPM) channels are calcium and magnesium ion transporters.
- TRPM subclasses TRPM2, TRPM6, TRPM7, and TRPM8 are notably expressed in liver cells.
- Hepatic ischemia-reperfusion (I/R) is a critical condition affecting liver function.
Purpose of the Study:
- To examine the effects of verapamil on TRPM2, TRPM6, TRPM7, and TRPM8 gene expression.
- To evaluate histopathological alterations in the liver following I/R injury and verapamil treatment.
- To investigate the role of specific TRPM channels in hepatic I/R injury.
Main Methods:
- A rat model of hepatic ischemia-reperfusion was established.
- Animals were divided into sham, verapamil, I/R, and I/R-verapamil groups.
- Gene expression was quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), and tissue damage was assessed via Hematoxylin and Eosin (HE) staining.
Main Results:
- TRPM2, TRPM6, TRPM7, and TRPM8 gene expression significantly increased in I/R and verapamil-treated groups compared to the sham group.
- Hepatocytes in the I/R group showed severe necrosis, degeneration, and hemorrhage.
- The I/R-verapamil group exhibited moderate necrosis, degeneration, and hemorrhage.
Conclusions:
- This study is the first to report on TRPM channel expression in a hepatic I/R rat model.
- TRPM2, TRPM6, TRPM7, and TRPM8 play a role in the pathophysiology of hepatic ischemia-reperfusion.
- Verapamil influences TRPM gene expression and liver histopathology during I/R injury.
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