Transcriptomic analysis of mouse cochleae suffering from gentamicin damage reveals the signalling pathways involved in hair cell regeneration
| Autor: | Lingling Jiang, Xinwen Zhang, Mei-Guang Zhang, Jie Bing, Chao Xi, Huanju Bai, Jincao Xu, Shaoju Zeng, Xi Wang, Weiqian Wang, Zhongming Han, Xue Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Biology Real-Time Polymerase Chain Reaction Bone morphogenetic protein Fibroblast growth factor Article Mice 03 medical and health sciences 0302 clinical medicine Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Regeneration Sonic hedgehog lcsh:Science Multidisciplinary Gene Expression Profiling Regeneration (biology) Transdifferentiation lcsh:R Wnt signaling pathway Cochlea Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein lcsh:Q Hair cell sense organs Gentamicins Signal transduction Chickens 030217 neurology & neurosurgery Neuroscience Signal Transduction |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-47051-5 |
| Popis: | There is a strong capacity for hair cell regeneration after damage in the inner ear of non-mammals. However, mammalian hair cells are substantially unable to regenerate. To obtain insights into the mechanism of this difference, we analyzed the transcriptomic changes in the mouse cochleae suffered from gentamicin damage and compared them with those in the chick cochleae suffered from the same damage. The results indicated that 2,230 genes had significantly differential expression between the gentamicin- and saline-treated mouse cochleae. Some of the differentially expressed genes were grouped into 265 signaling pathways, including the Notch, Wnt (Wingless and INT-1), Bmp (bone morphogenetic protein), FGF (fibroblast growth factor) and Shh (sonic hedgehog) pathways. Using pharmacological inhibitors or agonists of these pathways, the effects of these pathways on hair cell regeneration were further studied. The results indicated that Bmp alone and its coregulation with the Notch or Wnt signaling pathways increased the numbers of generated cells from transdifferentiation or proliferation in the mouse cochlea after damage, in addition to the reported coregulation of Notch and Wnt. Thus, this work indicates a new signaling pathway (Bmp) and its synergetic coregulation in mammalian hair cell regeneration, providing potential therapeutic targets to increase mammalian hair cell regeneration. |
| Databáze: | OpenAIRE |
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