ArticleCell death discovery2024
Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- The ILK-PINCH-parvin complex: a conserved primary adhesome regulating biological processes.Histochemistry and cell biology · 2025Review
- Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice.Journal of otology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells. Our goal of the present study was to investigate the mechanism underlying cochlear cell death in the Fscn2 knockout mice. Microarray analysis revealed upregulation of expression of PARVB, a local adhesion protein, in the inner ears of Fscn2 knockout mice at 8 weeks of age. Further studies showed increased levels of PARVB together with cleaved-Caspase9 and decreased levels of ILK, p-ILK, p-AKT, and Bcl-2 in the inner ears of Fscn2 knockout mice of the same age. Knockdown of Fscn2 in HEI-OCI cells led to decreased cell proliferation ability and migration rate, along with increased levels of PARVB and decreased levels of ILK, p-ILK, p-AKT, Bcl-2 and activated Rac1 and Cdc42. Overexpression of Fscn2 or inhibition of Parvb expression in HEI-OC1 cells promoted cell proliferation and migration, with increased levels of ILK, p-ILK, p-AKT, and Bcl-2. Finally, FSCN2 binds with PPAR-γ to reduce its nuclear translocation in HEI-OC1 cells, and inhibition of PPAR-γ by GW9662 decreased the level of PARVB and increased the levels of p-AKT, p-ILK, and Bcl-2. Our results suggest that FSCN2 negatively regulates PARVB expression by inhibiting the entry of PPAR-γ into the cell nucleus, resulting in inhibition of ILK-AKT related pathways and of cochlear cell survival in Fscn2 knockout mice. Our findings provide new insights and ideas for the prevention and treatment of genetic hearing loss.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.