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Research article
Li Li
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8591-0676
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Currently, the specific mechanism of estrogen (E2) in protecting presbycusis is not clear. This study aimed to investigate whether E2 could affect the apoptosis of capillary pericytes (PCs) of cochlear stria vascularis (SV) in aged C57BL/6J mice by regulating transmembrane member 16A (TMEM16A), such that it plays a protective role in presbycusis.
Methods: The model of C57BL/6J ovariectomized mice was established, and E2 was administered for 2 months. The hearing threshold was measured by auditory brainstem response (ABR). The changes in the cochlea were measured using hematoxylin-eosin (HE) and electron microscopy. qRT-PCR was used to examine the expression of TMEM16A and apoptosis-related protein mRNA. The PCs were cultured in vitro, and the cell senescence model was established by the continuous passage method. TMEM16A expression was assessed using immunofluorescence. Flow cytometry was performed to explore the apoptosis rate.
Results: The results of animal experiments showed that E2 intervention could reduce hearing loss and improve the atrophy of cochlear SV, loss of PC chromatin organelles, cytoplasmic swelling and nuclear porosity in aged mice. E2 also decreased the mRNA expression of TMEM16A, Caspase-3 and Bax in cochlear SV of aged mice and upregulated the expression of Bcl-2 mRNA. Cellular experiments showed that E2 could downregulate the expression of TMEM16A, and E2 or T16Ainh-A01(a specific blocker of TMEM16A) could reduce the apoptosis rate of PCs in aged mice.
Conclusions: E2 may inhibit the apoptosis of PCs through downregulating the expression of TMEM16A, which plays a protective role in presbycusis. This study may provide a novel potential treatment and prevention method for presbycusis.
Keywords
TMEM16A, pericytes, presbycusis, estrogen, apoptosis
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This is a preprint. It has not completed peer review.
Research article
Li Li
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8591-0676
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 20 Aug, 2020
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Molecular Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Currently, the specific mechanism of estrogen (E2) in protecting presbycusis is not clear. This study aimed to investigate whether E2 could affect the apoptosis of capillary pericytes (PCs) of cochlear stria vascularis (SV) in aged C57BL/6J mice by regulating transmembrane member 16A (TMEM16A), such that it plays a protective role in presbycusis.
Methods: The model of C57BL/6J ovariectomized mice was established, and E2 was administered for 2 months. The hearing threshold was measured by auditory brainstem response (ABR). The changes in the cochlea were measured using hematoxylin-eosin (HE) and electron microscopy. qRT-PCR was used to examine the expression of TMEM16A and apoptosis-related protein mRNA. The PCs were cultured in vitro, and the cell senescence model was established by the continuous passage method. TMEM16A expression was assessed using immunofluorescence. Flow cytometry was performed to explore the apoptosis rate.
Results: The results of animal experiments showed that E2 intervention could reduce hearing loss and improve the atrophy of cochlear SV, loss of PC chromatin organelles, cytoplasmic swelling and nuclear porosity in aged mice. E2 also decreased the mRNA expression of TMEM16A, Caspase-3 and Bax in cochlear SV of aged mice and upregulated the expression of Bcl-2 mRNA. Cellular experiments showed that E2 could downregulate the expression of TMEM16A, and E2 or T16Ainh-A01(a specific blocker of TMEM16A) could reduce the apoptosis rate of PCs in aged mice.
Conclusions: E2 may inhibit the apoptosis of PCs through downregulating the expression of TMEM16A, which plays a protective role in presbycusis. This study may provide a novel potential treatment and prevention method for presbycusis.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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