| First Author | Tang S | Year | 2021 |
| Journal | Exp Eye Res | Volume | 205 |
| Pages | 108485 | PubMed ID | 33582182 |
| Mgi Jnum | J:324867 | Mgi Id | MGI:6824156 |
| Doi | 10.1016/j.exer.2021.108485 | Citation | Tang S, et al. (2021) AQP5 regulates vimentin expression via miR-124-3p.1 to protect lens transparency. Exp Eye Res 205:108485 |
| abstractText | The pathogenesis of congenital cataract (CC), a major disease associated with blindness in infants, is complex and diverse. Aquaporin 5 (AQP5) represents an essential membrane water channel. In the present study, whole exome sequencing revealed a novel heterozygous missense mutation of AQP5 (c.152 T > C, p. L51P) in the four generations of the autosomal dominant CC (adCC) family. By constructing a mouse model of AQP5 knockout (KO) using the CRISPR/Cas9 technology, we observed that the lens of AQP5-KO mice showed mild opacity at approximately six months of age. miR-124-3p.1 expression was identified to be downregulated in the lens of AQP5-KO mice as evidenced by qRT-PCR analysis. A dual luciferase reporter assay confirmed that vimentin was a target gene of miR-124-3p.1. Organ-cultured AQP5-KO mouse lenses were showed increased opacity compared to those of WT mice, and vimentin expression was upregulated as determined by RT-PCR, western blotting, and immunofluorescence staining. After miR-124-3p.1 agomir was added, the lens opacity in WT mice and AQP5-KO mice decreased, accompanied by the downregulation of vimentin. AQP5-L51P increased vimentin expression of in human lens epithelial cells. Therefore, a missense mutation in AQP5 (c.152 T > C, p. L51P) was associated with adCC, and AQP5 could participate in the maintenance of lens transparency by regulating vimentin expression via miR-124-3p.1. |
