Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea

Zhang, Shasha; Zhang, Yuan; Dong, Ying; Guo, Lingna; Zhang, Zhong; Shao, Buwei; Qi, Jieyu; Zhou, Han; Zhu, Weijie; Yan, Xiaoqian; Hong, Guodong; Zhang, Liyan; Zhang, Xiaoli; Tang, Mingliang; Zhao, Chunjie; Gao, Xia; Chai, Renjie

doi:10.1007/s00018-019-03291-2

Cited by 104 publications

(99 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the auditory system, HCs and SGNs are very important for hearing ability; HCs convert the sound waves into electrical signals, and SGN transmit the electrical signals into the auditory cortex for hearing ability [29]. In a mammal's cochlea, HCs and SGNs are vulnerable for multiple damages, including noise, gene mutation, ototoxic drugs, inflammation, and aging [30][31][32][33][34]; while the mammal's cochlea only have very limited HC and SGN regeneration ability, majority of the damaged HC and SGN cannot be spontaneously regenerated [35][36][37][38][39][40][41]. Thus, hearing loss is usually irreversible, and AN may come from the damage of IHC and SGNs.…”

Section: Discussionmentioning

confidence: 99%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

View full text Add to dashboard Cite

To decipher the genotype-phenotype correlation of auditory neuropathy (AN) caused by AIFM1 variations, as well as the phenotype progression of these patients, exploring the potential molecular pathogenic mechanism of AN. A total of 36 families of individuals with AN (50 cases) with AIFM1 variations were recruited and identified by Sanger sequencing or next-generation sequencing; the participants included 30 patients from 16 reported families and 20 new cases. We found that AIFM1-positive cases accounted for 18.6% of late-onset AN cases. Of the 50 AN patients with AIFM1 variants, 45 were male and 5 were female. The hotspot variation of this gene was p.Leu344Phe, accounting for 36.1%. A total of 19 AIFM1 variants were reported in this study, including 7 novel ones. A follow-up study was performed on 30 previously reported AIFM1-positive subjects, 16 follow-up cases (53.3%) were included in this study, and follow-up periods were recorded from 1 to 23 years with average 9.75±9.89 years. There was no hearing threshold increase during the short-term follow-up period (1-10 years), but the low-frequency and high-frequency hearing thresholds showed a significant increase with the prolongation of follow-up time. The speech discrimination score progressed gradually and significantly along with the course of the disease and showed a more serious decline, which was disproportionately worse than the pure tone threshold. In addition to the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is also observed in AIFM1-related AN and affects females. In conclusion, we confirmed that AIFM1 is the primary related gene among late-onset AN cases, and the most common recurrent variant is p.Leu344Phe. Except for the X-linked recessive inheritance pattern, the X-linked dominant inheritance pattern is another probability of AIFM1-related AN, with females affected. Phenotypical features of AIFM1-related AN suggested that auditory dyssynchrony progressively worsened over time.

show abstract

Section: Discussionmentioning

confidence: 99%

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Wang

Dai

et al. 2020

Neural Plasticity

View full text Add to dashboard Cite

show abstract

“…Regarding plasticity and reconstruction of neural network after hearing injury, Ctpb2 was usually used to label the synapse, and the number of innervated synapses was compared to assess the structure and function of neural connections (Zhang et al, 2019). Our results suggest that blebbistatin has a good protective effect on synaptic damage caused by neomycin in HCs.…”

Section: Discussionmentioning

confidence: 84%

Blebbistatin Inhibits Neomycin-Induced Apoptosis in Hair Cell-Like HEI-OC-1 Cells and in Cochlear Hair Cells

Gao

Cheng

Wang

et al. 2020

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Aging, noise, and ototoxic drug-induced hair cell (HC) loss are the major causes of sensorineural hearing loss. Aminoglycoside antibiotics are commonly used in the clinic, but these often have ototoxic side effects due to the accumulation of oxygen-free radicals and the subsequent induction of HC apoptosis. Blebbistatin is a myosin II inhibitor that regulates microtubule assembly and myosin-actin interactions, and most research has focused on its ability to modulate cardiac or urinary bladder contractility. By regulating the cytoskeletal structure and reducing the accumulation of reactive oxygen species (ROS), blebbistatin can prevent apoptosis in many different types of cells. However, there are no reports on the effect of blebbistatin in HC apoptosis. In this study, we found that the presence of blebbistatin significantly inhibited neomycin-induced apoptosis in HC-like HEI-OC-1 cells. We also found that blebbistatin treatment significantly increased the mitochondrial membrane potential (MMP), decreased ROS accumulation, and inhibited pro-apoptotic gene expression in both HC-like HEI-OC-1 cells and explant-cultured cochlear HCs after neomycin exposure. Meanwhile, blebbistatin can protect the synaptic connections between HCs and cochlear spiral ganglion neurons. This study showed that blebbistatin could maintain mitochondrial function and reduce the ROS level and thus could maintain the viability of HCs after neomycin exposure and the neural function in the inner ear, suggesting that blebbistatin has potential clinic application in protecting against ototoxic drug-induced HC loss.

show abstract

“…The Foxg1 gene is a dose-sensitive gene, it can antagonize the proapoptotic effect of Foxo3 [22] and promotes hepatocellular carcinoma epithelial-mesenchymal transition [23]. As Shasha Zhang's reported, knocking out the Foxg1 gene will increase differentiation of newborn mouse cells [24]. Studies have found that cyclin D plays an important role in cell proliferation, which has three subfamilies: cyclin D1, cyclin D2 and cyclin D3.…”

Section: Introductionmentioning

confidence: 99%

GDF-5 promotes Epidermal Stem Cells proliferation via Foxg1-cyclin D1 signaling

Zhao

Bian²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Objective: Epidermal stem cells (EpSCs) can self-renew and are responsible for the long-term maintenance of the skin, it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. Here, we studied the effects of GDF-5 on mouse EpSCs proliferation mechanism in wound healing. Methods: Firstly, the effects of GDF-5 on EpSCs proliferation was tested by using CCK8 reagent and PCNA expression was analysed by western blotting. Secondly, we screened genes that promote EpSCs proliferation in the FOX family and cyclin by qPCR, and further analysed the protein expression level of the selected genes by Western blotting. Thirdly, siRNA plasmids and pAdEasy adenovirus were transfected or infected, respectively, into mouse EpSCs to detect the effect of target genes on GDF-5 induced cell proliferation. Furthermore, a deep partial thickness burn mouse model was used in which GDF-5 induced EpSCs proliferation was detected by immunohistochemical. Finally, the relationships target genes were analysed by qPCR, immunoblotting and dual luciferase reporter gene detection. Results: We discovered that 100 ng/ml recombinant mouse GDF-5 was the optimal concentration for promoting mouse EpSCs proliferation. Through preliminary screening by qPCR, we found that Foxg1 and cyclin D1 could be the downstream molecules of GDF-5, and the results were confirmed by Western blotting. And the effect of GDF-5 on mouse EpSCs proliferation was regulated by Foxg1/cyclin D1 in vitro and in vivo. Besides, GDF-5 induced transcription of cyclin D1 was regulated by Foxg1-mediated cyclin D1 promoter activity.Conclusion: This paper showed that GDF-5 promotes mouse EpSCs proliferation via Foxg1-cyclin D1 signal pathway. It is suggested that GDF-5 may be a new approach to yield EpSCs for wound healing.

show abstract

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea

Cited by 104 publications

References 96 publications

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population

Blebbistatin Inhibits Neomycin-Induced Apoptosis in Hair Cell-Like HEI-OC-1 Cells and in Cochlear Hair Cells

GDF-5 promotes Epidermal Stem Cells proliferation via Foxg1-cyclin D1 signaling

Contact Info

Product

Resources

About