Molecular mechanism of hypoxia and alpha-ketoglutaric acid on collagen expression in scleral fibroblasts
| Autor: | Yun Sun, Zhuo-Zheng Li, Jing Yang, Ya-Ru Sha, Xin-Yu Hou, Hong Fu, Jia-Yin Li, Shu-Chang Bai, Yong-Fang Xie, Guo-Hui Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | International Journal of Ophthalmology, Vol 17, Iss 10, Pp 1780-1790 (2024) |
| Druh dokumentu: | article |
| ISSN: | 2222-3959 2227-4898 |
| DOI: | 10.18240/ijo.2024.10.03 |
| Popis: | AIM: To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid (α-KG) on scleral collagen expression. METHODS: Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness (ChT) during myopia. The establishment of a hypoxic myopia model (HYP) for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia and α-KG on collagen expression were demonstrated by Sirius red staining. Transcriptome analysis was used to verify the genes and pathways that hypoxia and α-KG affect collagen expression. Finally, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used for reverse verification. RESULTS: Meta-analysis results aligned with clinical statistics, revealing a thinning of ChT, leading to scleral hypoxia. Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group, showed that hypoxia reduced collagen expression in scleral fibroblasts, while α-KG can elevated collagen expression under HYP conditions. Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia and α-KG affect scleral collagen expression and the results were verified by RT-qPCR. CONCLUSION: The potential molecular mechanisms through which hypoxia and α-KG influencing myopia is unraveled and three novel genes TLCD4, TBC1D4, and EPHX3 are identified. These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression. |
| Databáze: | Directory of Open Access Journals |
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