Abstract
Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration.
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Funding
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2019R1F1A1059231). This study was conducted with support from the Rural Development Administration (PJ014155052019).
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SJK and KWB: conception and design, animal experiment, data collection, figure preparation, and manuscript writing. YKJ, JSK, and BGK: animal experiment, in vitro experiment, and histological experiment. HSY, JSP, and JIY: conception and financial support. JIY: conception and design, data interpretation, and final approval of the manuscript. All the authors have reviewed and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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The animal studies were approved by the Institutional Animal Care and Use and Committee of Pusan National University (approval number, PNU-2019-2358).
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Key Points
• By natural aging, the expression of AQP1 increases, AQP4 decreases, and AQP7 does not appear to change.
• In aged mice, expression of AQP1 significantly decreased gene expression due to acute water restriction, but protein expression was not.
• AQP1 overexpression inhibits myotube differentiation and knockdown promotes myotube differentiation.
Supplementary information
Fig. S1
AQPs expression on the IHC microscopic images of GA muscle sections. Each arrow indicate AQP1 stained location. Scale bar represents 60 μm (PNG 2293 kb)
Fig. S2
AQPs expression on the IHC microscopic images of TA muscle sections. The arrows indicate AQP1 stained locations. Scale bar represents 60 μm (PNG 2237 kb)
Fig. S3
Transfection efficiency of Aqp1. (A) Aqp1 overexpression and (B) Aqp1 knockdown. Transfection efficiency was analyzed by quantitative real-time RT-PCR. All data are presented as the mean ± S.D.; vs. control group, **p < 0.01, ****p < 0.0001 (PNG 31 kb)
Fig. S4
Myotube differentiation according to passage of the day after transfection. Each arrow indicates differentiated myotube. Scale bar represents 1150 μm (PNG 6066 kb)
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Kim, SJ., Baek, KW., Jung, YK. et al. Changes in aquaporins expression due to acute water restriction in naturally aging mice. J Physiol Biochem 79, 71–81 (2023). https://doi.org/10.1007/s13105-022-00921-5
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DOI: https://doi.org/10.1007/s13105-022-00921-5