Aqp5, short for aquaporin 5, is a selective transmembrane protein primarily responsible for water and small molecule transport. It has been implicated in various biological processes and diseases. Aqp5 is involved in maintaining normal physiological functions in tissues such as salivary glands, where its level is regulated by factors like parasympathetic nerve activity and is associated with amylase secretion [2].

In disease contexts, Aqp5 deficiency promotes the senescence of lens epithelial cells through mitochondrial dysfunction, which may provide new insights for cataract treatment [3]. In congenital cataract, a missense mutation in Aqp5 was associated with autosomal dominant congenital cataract, and Aqp5 could maintain lens transparency by regulating vimentin expression via miR-124-3p.1 [4]. In cancer, Aqp5 is specifically highly expressed in gastric cancer stem cells, promoting their sphere formation, proliferation, migration, and invasion both in vitro and in vivo. It coordinates with LGR5 to synergistically promote tumorigenesis and activates autophagy through inducing LC3I/LC3II transformation and regulating ULK1 ubiquitination [1]. Also, in breast cancer, Aqp5 overexpression was observed in 36% of tissue samples, and its strong expression was positively correlated with tumor grade and more frequent in ER/PR-negative cases, being an independent marker for worse clinical outcomes [5].

In conclusion, Aqp5 plays essential roles in normal physiological functions and disease-related processes. Gene knockout models, especially in the context of lens epithelial cells and in relation to cataracts, as well as in cancer research, have provided valuable insights into Aqp5's functions. These studies help us better understand the biological significance of Aqp5 and its potential as a therapeutic target in related diseases.

References:

1. Zhao, Rou, He, Baoyu, Bie, Qingli, Xiong, Huabao, Zhang, Bin. 2022. AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination. In Journal of experimental & clinical cancer research : CR, 41, 322. doi:10.1186/s13046-022-02532-w. https://pubmed.ncbi.nlm.nih.gov/36372898/

2. Hosoi, Kazuo, Yao, Chenjuan, Hasegawa, Takahiro, Yoshimura, Hiroshi, Akamatsu, Tetsuya. 2020. Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions. In International journal of molecular sciences, 21, . doi:10.3390/ijms21041182. https://pubmed.ncbi.nlm.nih.gov/32053992/

3. Zhang, Kaier, Di, Guohu, Li, Bin, Wang, Dianqiang, Chen, Peng. 2023. AQP5 deficiency promotes the senescence of lens epithelial cells through mitochondrial dysfunction. In Biochemical and biophysical research communications, 680, 184-193. doi:10.1016/j.bbrc.2023.09.051. https://pubmed.ncbi.nlm.nih.gov/37742347/

4. Tang, Suzhen, Di, Guohu, Hu, Shaohua, Dai, Yunhai, Chen, Peng. 2021. AQP5 regulates vimentin expression via miR-124-3p.1 to protect lens transparency. In Experimental eye research, 205, 108485. doi:10.1016/j.exer.2021.108485. https://pubmed.ncbi.nlm.nih.gov/33582182/

5. Jang, Se Jin, Moon, Chulso. 2023. Aquaporin 5 (AQP5) expression in breast cancer and its clinicopathological characteristics. In PloS one, 18, e0270752. doi:10.1371/journal.pone.0270752. https://pubmed.ncbi.nlm.nih.gov/36706090/