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Updated: May 5, 2026
A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection
Published on: February 2, 2022
Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation
Zhe Meng1, Rui Cao, Yongzhi Wang
1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China, mengzhe@whu.edu.cn.
Purpose:
The aim of this study was to investigate the effect of renal cortex transient receptor potential melastatin 7 (TRPM7) suppression on renal ischemia reperfusion injury induced by transplantation in mice.
Methods:
M7shRNA was used to decrease the expression of TRPM7 in NRK-52e cells. The mice were subjected to renal intra-parenchymal injection with lentivirus containing M7shRNA to produce hypo-expression of TRPM7 in renal cortex. Cell hypoxia mode and syngeneic renal transplantation in vivo were established. Then the effects of M7shRNA were measured by fluorescent probe for reactive oxygen species (ROS), intracellular calcium and magnesium; Western blot was applied for p38-MAPKs and Bax expression in cell studies. In vivo studies, mice were killed 24 h, 48 h, 72 h, 7 days and 21 days, respectively, after transplantation and the kidneys were dissected. Serum creatinine was measured, and the H&E, Masson's trichrome staining, TUNEL, Kim-1 and α-smooth muscle actin were used to evaluate pathological change.
Results:
In cell model of hypoxia, the level of ROS in NRK-52e-M7shRNA was significantly lower than that in both NRK-52e and NRK-52e control cells, while the activation of p38-MAPKs was limited. In renal transplanted mice, renal function of M7shRNA group was conspicuously better than PBS- and vector-control-treated group. The histological examination showed that renal tubule injury and interstitial fibrosis were lower in M7shRNA-treated group compared with PBS and vector-control group.
Conclusions:
Suppression of renal cortex TRPM7 could alleviate kidney injury induced by transplantation in mice. The mechanism may involve reducing the early stage of ischemia reperfusion injury by inhibition of intracellular Ca(2+), Mg(2+) and ROS.
Insights
Suppressing renal cortex transient receptor potential melastatin 7 (TRPM7) significantly reduced kidney injury after transplantation in mice. This protective effect may stem from inhibiting intracellular calcium, magnesium, and reactive oxygen species during ischemia reperfusion.
Area of Science:
- Nephrology
- Molecular Biology
- Transplantation Immunology
Background:
- Renal ischemia reperfusion injury (IRI) is a major complication following kidney transplantation.
- Transient receptor potential melastatin 7 (TRPM7) is a channel protein implicated in cellular stress responses.
- Understanding TRPM7's role in renal IRI is crucial for developing protective strategies.
Purpose of the Study:
- To investigate the therapeutic potential of suppressing renal cortex TRPM7 in a mouse model of kidney transplantation-induced IRI.
- To elucidate the underlying mechanisms by which TRPM7 inhibition affects renal IRI.
Main Methods:
- TRPM7 expression was suppressed in renal cells (NRK-52e) and in mouse renal cortex using M7shRNA lentivirus.
- In vitro: Hypoxia model to assess reactive oxygen species (ROS), intracellular calcium (Ca2+), magnesium (Mg2+), p38-MAPKs, and Bax.
- In vivo: Syngeneic renal transplantation model in mice to evaluate renal function, histology (H&E, Masson's trichrome), apoptosis (TUNEL), and fibrosis markers (Kim-1, α-smooth muscle actin).
Main Results:
- TRPM7 suppression reduced ROS levels and p38-MAPK activation in hypoxic renal cells.
- Mice treated with M7shRNA exhibited significantly improved renal function compared to control groups post-transplantation.
- Histological analysis revealed decreased renal tubule injury and interstitial fibrosis in the M7shRNA-treated group.
Conclusions:
- Suppression of renal cortex TRPM7 effectively alleviates kidney injury following transplantation in mice.
- The protective mechanism likely involves the inhibition of intracellular Ca2+, Mg2+, and ROS, mitigating early-stage IRI.
- Targeting TRPM7 presents a promising therapeutic avenue for preventing renal IRI in transplantation.
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