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Changes in expression of klotho affect physiological processes, diseases, and cancer
Nguyen Thi Xuan1, Nong Van Hai1
1Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Iranian Journal of Basic Medical Sciences
|January 27, 2018
Summary
Klotho (KL) protein regulates calcium channels and cell migration, impacting aging and cancer. Its expression is controlled by the PI3K pathway in dendritic cells, influencing Orai3 channel activity.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Klotho (KL) is a transmembrane protein involved in aging, cancer, and inflammation.
- KL regulates insulin/IGF-1 signaling, growth hormone secretion, and calcium channel activity.
- Genetic studies link KL gene hypermethylation to aging, disease, and cancer risk.
Purpose of the Study:
- To investigate the role of Klotho in regulating calcium influx and dendritic cell migration.
- To explore the involvement of the phosphoinositide 3-kinase (PI3K) pathway in KL expression.
- To determine the effect of KL downregulation on specific calcium channel expression in dendritic cells.
Main Methods:
- Utilized siRNA knockdown to downregulate KL expression in bone marrow-derived dendritic cells (BMDCs).
- Quantified changes in calcium channel expression (Orai1, Orai2, Orai3, TRPV5, TRPV6) in KL-silenced BMDCs.
- Investigated the regulation of KL expression via the PI3K pathway in DCs.
Main Results:
- KL modulates extracellular calcium influx and CCL21-dependent dendritic cell migration.
- KL expression in DCs is regulated by the PI3K signaling pathway.
- Downregulation of KL significantly reduced Orai3 calcium channel expression in BMDCs, but not Orai1, Orai2, TRPV5, or TRPV6.
Conclusions:
- KL plays a crucial role in regulating cellular functions, including calcium influx and cell migration, through the PI3K pathway.
- KL influences the expression of specific calcium channels, notably Orai3, in dendritic cells.
- Further research is needed to fully elucidate KL's function in organismic and cellular processes via PI3K signaling and calcium channel regulation.
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