Dataset Information

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice.

ABSTRACT:

Objectives

To investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear.

Materials and methods

Postnatal day 1 wild-type or neomycin-damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high-throughput RNA-sequencing was used to measure gene expression levels.

Results

We found that DBZ promoted SC proliferation and HC regeneration in a dose-dependent manner in both normal and damaged cochleae. In addition, most of the newly regenerated HCs induced by DBZ had visible and relatively mature stereocilia bundle structures. Finally, RNA sequencing detected the differentially expressed genes between DBZ treatment and controls, and interaction networks were constructed for the most highly differentially expressed genes.

Conclusions

Our study demonstrates that DBZ can significantly promote SC proliferation and increase the number of mitotically regenerated HCs with relatively mature stereocilia bundles in the neonatal mouse cochlea by inhibiting Notch signalling and activating Wnt signalling, suggesting the DBZ might be a new therapeutic target for stimulating HC regeneration.

SUBMITTER: Wu J

PROVIDER: S-EPMC7507434 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice.

Wu Jingfang J Dong Xinran X Li Wen W Zhao Liping L Zhou Li L Sun Shan S Li Huawei H

Cell proliferation 20200717 9

<h4>Objectives</h4>To investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear.<h4>Materials and methods</h4>Postnatal day 1 wild-type or neomycin-damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high-throughput RNA-sequencing was used to measure gene expression levels.<h4>Results</h4>We found that DBZ p ...[more]

PMID: 32677724

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Project description:Myeloid-derived growth factor (Mydgf), a paracrine protein secreted by bone marrow-derived monocytes and macrophages, was found to protect against cardiac injury following myocardial infarction (MI) in adult mice. We speculated that Mydgf might improve heart function via myocardial regeneration, which is essential for discovering the target to reverse heart failure. Methods: Two genetic mouse lines were used: global Mydgf knockout (Mydgf-KO) and Mydgf-EGFP mice. Two models of cardiac injury, apical resection was performed in neonatal and MI was performed in adult mice. Quantitative reverse transcription-polymerase chain reaction, western blot and flow cytometry were performed to study the protein expression. Immunofluorescence was performed to detect the proliferation of cardiomyocytes. Heart regeneration and cardiac function were evaluated by Masson's staining and echocardiography, respectively. RNA sequencing was employed to identify the key involved in Mydgf-induced cardiomyocyte proliferation. Mydgf recombinant protein injection was performed as a therapy for cardiac repair post MI in adult mice. Results: Mydgf expression could be significantly induced in neonatal mouse hearts after cardiac injury. Unexpectedly, we found that Mydgf was predominantly expressed by endothelial cells rather than macrophages in injured neonatal hearts. Mydgf deficiency impeded neonatal heart regeneration and injury-induced cardiomyocyte proliferation. Mydgf recombinant protein promoted primary mouse cardiomyocyte proliferation. Employing RNA sequencing and functional verification, we demonstrated that c-Myc/FoxM1 pathway mediated Mydgf-induced cardiomyocyte expansion. Mydgf recombinant protein improved cardiac function in adult mice after MI injury with inducing cardiomyocyte proliferation. Conclusion: Mydgf promotes cardiomyocyte proliferation by activating c-Myc/FoxM1 pathway and improves heart regeneration both in neonatal and adult mice after cardiac injury, providing a potential target to reverse cardiac remodeling and heart failure.

Dataset Information

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice.

Objectives

Materials and methods

Results

Conclusions

Publications

Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice.

Similar Datasets

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