Reactive Oxygen Species Downregulate Transient Receptor Potential Melastatin 6 Expression Mediated by the Elevation of miR-24-3p in Renal Tubular Epithelial Cells
Background: A low level of serum magnesium ion (Mg2+) is associated with type 2 diabetes mellitus (T2D). However, the molecular mechanism of Mg2+ deficiency has not been fully clarified. The current study sought to assesses the effect of reactive oxygen species on the expression of Mg2+ channels and miRNA. Methods: The expression of Mg2+ channels and miRNA were examined by real-time polymerase chain reaction. Intracellular Mg2+ concentration was measured by Magnesium Green fluorescence measurement. Results: The mRNA level of transient receptor potential melastatin 6 (TRPM6), which functions as Mg2+ influx channel in the distal convoluted tubule (DCT) of the kidney, was decreased by glycated albumin (GA), but not by insulin in rat renal tubule-derived NRK-52E cells. The mRNA levels of TRPM7, a homologue of TRPM6, and CNNM2, a Mg2+ efflux transporter located at the basolateral membrane of DCT, were changed by neither GA nor insulin. The generation of reactive oxygen species (ROS) was increased by GA. Hydrogen peroxide (H2O2) dose-dependently decreased TRPM6 mRNA, but it inversely increased the reporter activity of TRPM6. H2O2 accelerated the degradation of TRPM6 mRNA in actinomycin D assay without affecting TRPM7 and CNNM2 mRNA expressions. Nine miRNAs were considered as candidates for the regulator of stability of TRPM6 mRNA. Among them, miR-24-3p expression was increased by H2O2. The H2O2-induced reduction of TRPM6 mRNA was rescued by miR-24-3p siRNA. Magnesium Green fluorescence measurement showed that Mg2+ influx is suppressed by H2O2, which was rescued by an antioxidant and miR-24-3p siRNA. Conclusions: We suggest that GA decreases TRPM6 expression mediated by the elevation of ROS and miR-24-3p in renal tubular epithelial cells of T2D.
机构:
Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Nunez-Villena, Felipe
Becerra, Alvaro
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Becerra, Alvaro
Echeverria, Cesar
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Echeverria, Cesar
Briceno, Nicolas
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Briceno, Nicolas
Porras, Omar
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Univ Chile, Fac Med, Ctr Estudios Mol Celula, CEMC, Santiago 7, Chile
Univ Chile, ICBM, Inst Ciencias Biomed, Santiago 7, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Porras, Omar
Armisen, Ricardo
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Univ Chile, Fac Med, Ctr Estudios Mol Celula, CEMC, Santiago 7, Chile
Univ Chile, ICBM, Inst Ciencias Biomed, Santiago 7, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Armisen, Ricardo
Varela, Diego
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Univ Chile, Fac Med, Ctr Estudios Mol Celula, CEMC, Santiago 7, Chile
Univ Chile, ICBM, Inst Ciencias Biomed, Santiago 7, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Varela, Diego
Montorfano, Ignacio
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Montorfano, Ignacio
Sarmiento, Daniela
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Sarmiento, Daniela
Simon, Felipe
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Univ Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
Univ Andres Bello, Fac Med, Santiago 8370146, ChileUniv Andres Bello, Dept Ciencias Biol, Fac Ciencias Biol, Santiago 8370146, Chile
机构:
Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Wang, Yanxia
Ding, Min
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Ding, Min
Chaudhari, Sarika
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Chaudhari, Sarika
Ding, Yanfeng
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Ding, Yanfeng
Yuan, Joseph
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Yuan, Joseph
Stankowska, Dorota
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Univ N Texas, Hlth Sci Ctr, Dept Cell Biol, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Stankowska, Dorota
He, Shaoqing
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Univ N Texas, Hlth Sci Ctr, Dept Cell Biol, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
He, Shaoqing
Krishnamoorthy, Raghu
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Univ N Texas, Hlth Sci Ctr, Dept Cell Biol, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Krishnamoorthy, Raghu
Cunningham, Joseph T.
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Cunningham, Joseph T.
Ma, Rong
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Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Ft Worth, TX 76107 USAUniv N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX 76107 USA
机构:
Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Hebei Univ Engn, Affiliated Hosp, Med Coll, Dept Anat, Handan 056002, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Hou, Xin
Xiao, Haitao
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Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Xiao, Haitao
Zhang, Yanhong
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机构:
Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Zhang, Yanhong
Zeng, Xixi
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Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Zeng, Xixi
Huang, Mengjun
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Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huang, Mengjun
Chen, Xiaoyun
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机构:
First Hosp Wuhan, Dept Pathol, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Chen, Xiaoyun
Birnbaumer, Lutz
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机构:
Catholic Univ Argentina, Inst Biomed Res BIOMED, C1107AFF, Buenos Aires, DF, Argentina
NIEHS, Neurobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USAHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Birnbaumer, Lutz
Liao, Yanhong
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Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China
Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Wuhan 430030, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Tongji Med Coll, Dept Anat, Wuhan 430030, Hubei, Peoples R China