Protection from noise-induced hearing loss with Src inhibitors

Bielefeld, Eric C.

doi:10.1016/j.drudis.2015.01.010

Cited by 6 publications

(3 citation statements)

References 57 publications

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“…Dusp6 is expressed in the otic region during embryonic development and acts as a negative feedback regulator of FGF signaling (Urness et al, 2008). Rhoa , Wnt5a , Src , Vangl2 , and Wif1 mediate planar cell polarity in the inner ear (Dabdoub et al, 2003; Qian et al, 2007; Copley et al, 2013; Andreeva et al, 2014; Sai et al, 2014), and Src inhibitors protect HCs from noise-induced damage (Bielefeld, 2015). Fgf9 participates in regulating the number of cochlear progenitors and the length of the cochlea through mesenchymal FGFR signaling (Pirvola et al, 2004; Huh et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Cheng

Guo

Lü

et al. 2017

Front. Mol. Neurosci.

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Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Cheng

Guo

Lü

et al. 2017

Front. Mol. Neurosci.

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“…Another pharmacological, cochlear drug delivery approach employed by Eric Bielefeld’s team for achieving protection from the deleterious effects of loud noise is to utilize Src protein tyrosine kinase (PTK) inhibitors as protective or therapeutic treatments (Bielefeld 2015). They employed subcutaneous injection of PTK inhibitors in chinchillas before noise exposure and showed similar protective effects to N-acetyl cysteine (NAC) as well as significant otoprotective effects when this compound was injected in combination with NAC.…”

Section: Systemic Effects: Cochlear Drug Delivery Yields Oto-protectimentioning

confidence: 99%

Animal model studies yield translational solutions for cochlear drug delivery

et al. 2018

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The field of hearing and deafness research is about to enter an era where new cochlear drug delivery methodologies will become more innovative and plentiful. The present report provides a representative review of previous studies where efficacious results have been obtained with animal models, primarily rodents, for protection against acute hearing loss such as acoustic trauma due to noise overexposure, antibiotic use and cancer chemotherapies. These approaches were initiated using systemic injections or oral administrations of otoprotectants. Now, exciting new options for local drug delivery, which opens up the possibilities for utilization of novel otoprotective drugs or compounds that might not be suitable for systemic use, or might interfere with the efficacious actions of chemotherapeutic agents or antibiotics, are being developed. These include interesting use of nanoparticles (with or without magnetic field supplementation), hydrogels, cochlear micropumps, and new transtympanic injectable compounds, sometimes in combination with cochlear implants.

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“…Noise can cause a wide spectrum of metabolic and mechanical damages in the cochlea leading to hearing loss. Noise-induced hearing loss is one of the significant causes of acquired hearing loss which is often preventable [ 28 , 29 ]. Noise and other factors that affect hearing in healthy individuals are also likely to affect patients with RA, even though no studies were found evaluating these subjects specifically in RA patients.…”

Section: Environmental Factorsmentioning

confidence: 99%

Is Hearing Impairment Associated with Rheumatoid Arthritis? A Review

Emamifar¹,

Bjøerndal²,

Hansen³

2016

TORJ

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Background:Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects 1% of the population. The auditory system may be involved during the course of disease; however the association of RA and hearing impairment has not been clearly defined. Objective: The objective of this review is to evaluate published clinical reports related to hearing impairment in patients with RA. Furthermore, we discuss possible pathologies and associated factors as well as new treatment modalities. Method:A thorough literature search was performed using available databases including Pubmed, Embase, Cochrane and ComDisDome to cover all relative reports. The following keywords were used: hearing loss, hearing difficulties, hearing disorders, hearing impairment, sensorineural hearing loss, conductive hearing loss, mixed hearing loss, autoimmune hearing loss, drug ototoxicity, drug-induced hearing loss, hearing test, audiometry, auditory dysfunction and rheumatoid arthritis. Conclusion:Based on our review it can be postulated that patients with RA are at higher risk of hearing impairment compared to healthy subjects in their course of the disease. The hearing impairment in RA seems to be a multifactorial condition; however the mechanisms of injury, as well as the relative risk factors, are not completely clear. This review can aid to clarify this condition and is a guide for further evaluation. To the best of our knowledge, this is the first review of hearing impairment in RA.

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Protection from noise-induced hearing loss with Src inhibitors

Cited by 6 publications

References 57 publications

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

Animal model studies yield translational solutions for cochlear drug delivery

Is Hearing Impairment Associated with Rheumatoid Arthritis? A Review

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