Vnn1-KO Mouse

Vnn1, also known as Vanin1, is an exogenous enzyme with pantetheinase activity. It degrades pantetheine to pantothenate (vitamin B5, a precursor of coenzyme A (CoA) biosynthesis) and cysteamine, thus participating in CoA metabolism. It has drawn attention for its crosstalk with metabolism and oxidative stress, and is a key component in disease progression [2,4].

In a VNN1 knockout (KO) mouse model, after ischemia/reperfusion (I/R) injury, the recovery of serum creatinine and blood urea nitrogen levels was accelerated, renal fibrosis was inhibited, and senescence of renal tubular cells was suppressed. This suggests that VNN1 promotes the acute kidney injury-chronic kidney disease (AKI-CKD) transition via inducing senescence of renal tubular cells by activating RB1 expression and phosphorylation [3]. In another study, VIVA mouse transgenic model, which specifically overexpresses Vnn1 on intestinal epithelial cells, was resistant to experimentally induced colitis. The pantetheinase activity of Vnn1 enhanced CoA regeneration and metabolic adaptation of colonocytes, and favored microbiota-dependent production of short chain fatty acids [1].

In conclusion, Vnn1, through its pantetheinase activity, is involved in important metabolic processes. The use of KO and transgenic mouse models has revealed its role in diseases such as colitis, AKI-CKD transition, providing insights into disease mechanisms and potential therapeutic targets related to these conditions.

References:

1. Millet, Virginie, Gensollen, Thomas, Maltese, Michael, Naquet, Philippe, Galland, Franck. 2022. Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis. In Gut, 72, 1115-1128. doi:10.1136/gutjnl-2021-325792. https://pubmed.ncbi.nlm.nih.gov/36175116/

2. Yu, Hao, Cui, Yuying, Guo, Fangyue, Dong, Deshi, Xiang, Hong. 2023. Vanin1 (VNN1) in chronic diseases: Future directions for targeted therapy. In European journal of pharmacology, 962, 176220. doi:10.1016/j.ejphar.2023.176220. https://pubmed.ncbi.nlm.nih.gov/38042463/

3. Chen, Jia, Lu, Hongxiang, Wang, Xiaoyue, He, Yani, Chen, Kehong. . VNN1 contributes to the acute kidney injury-chronic kidney disease transition by promoting cellular senescence via affecting RB1 expression. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22472. doi:10.1096/fj.202200496RR. https://pubmed.ncbi.nlm.nih.gov/35959877/

4. Naquet, Philippe, Pitari, Giuseppina, Duprè, Sylvestro, Galland, Franck. . Role of the Vnn1 pantetheinase in tissue tolerance to stress. In Biochemical Society transactions, 42, 1094-100. doi:10.1042/BST20140092. https://pubmed.ncbi.nlm.nih.gov/25110008/