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TRPM7 promotes lipopolysaccharide-induced inflammatory dysfunction in renal tubular epithelial cells
Yan Sun1, Xiaobing Chen1, Yongpeng Xie1
1Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China.
Background:
Sepsis-associated acute kidney injury (S-AKI) has been reported to affect 30%-50% of all sepsis patients; this condition is associated with a notable fatality rate. Following lipopolysaccharide (LPS) stimulation, the expression of transient receptor potential cation channel subfamily M member 7 (TRPM7), a nonselective cation channel expressed by the renal tubular epithelial cells (RTECs) was found to be upregulated. We aimed to determine how TRPM7 functions in S-AKI.
Methods:
To establish an in vitro model of S-AKI, RTECs were treated with LPS. The effect of TRPM7 knockdown on cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress was studied. The binding site between Kruppel-like factor 2 (KLF2) and TRPM7 was predicted using JASPAR. The influence of KLF2 on the regulatory roles of TRPM7 in cells, as well as the effect of their knockdown on the MAPK signaling pathway, was investigated.
Results:
TRPM7 was upregulated in LPS-treated cells, and knocking improved cell viability, reduced LDH levels, and minimized apoptosis, inflammation, and oxidative stress. KLF2 was shown to be associated with TRPM7 and its level decreased in LPS-treated cells. KLF2 knockdown increased TRPM7 expression and reversed the effects of TRPM7 knockdown in LPS-treated cells, including suppression of p38 MAPK, ERK1/2, and JNK activation.
Conclusion:
Taken together, our results show that TRPM7 is negatively regulated by KLF2 and promotes LPS-induced inflammatory dysfunction by activating the MAPK pathway in RTECs. The theoretical foundation for the prevention and management of S-AKI is laid out in this article.
Insights
Sepsis-associated acute kidney injury involves increased TRPM7 channel activity, which is negatively regulated by KLF2. Targeting TRPM7 may offer new treatments for sepsis-induced kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Sepsis-associated acute kidney injury (S-AKI) affects 30-50% of sepsis patients, carrying a high mortality rate.
- Lipopolysaccharide (LPS) stimulation upregulates the expression of TRPM7, a cation channel in renal tubular epithelial cells (RTECs).
Purpose of the Study:
- To investigate the role of TRPM7 in S-AKI.
- To elucidate the regulatory mechanism of TRPM7 by KLF2 in LPS-induced RTECs.
Main Methods:
- An in vitro S-AKI model was established using LPS-treated RTECs.
- TRPM7 and KLF2 knockdown experiments were performed.
- Cell viability, LDH release, apoptosis, inflammation, oxidative stress, and MAPK signaling pathway activation were assessed.
Main Results:
- TRPM7 upregulation was observed in LPS-treated RTECs.
- TRPM7 knockdown improved cell viability and reduced LDH release, apoptosis, inflammation, and oxidative stress.
- KLF2 negatively regulates TRPM7, and KLF2 knockdown exacerbated S-AKI phenotypes by increasing TRPM7 expression and activating the MAPK pathway.
Conclusions:
- TRPM7 promotes LPS-induced inflammatory dysfunction in RTECs via MAPK pathway activation.
- KLF2 negatively regulates TRPM7, suggesting a potential therapeutic target for S-AKI.
- This study provides a theoretical basis for S-AKI prevention and management.
