Padi2, short for peptidyl arginine deiminase 2, is an enzyme that catalyzes the post-translational conversion of peptidyl-arginine to peptidyl-citrulline in a process called citrullination. This process is involved in multiple biological functions, including transcriptional regulation, immune response, and cell differentiation. Padi2-related pathways have been associated with various diseases, highlighting its biological importance. Genetic models, such as gene knockout mouse models, are valuable for studying its functions [3,4,6].

In urothelial cancer, icaritin inhibits the progression by suppressing Padi2-mediated neutrophil infiltration and neutrophil extracellular trap formation, showing its role in tumor-related inflammation [1]. In sepsis-induced acute lung injury, the deletion of Padi2 and Padi4 in double knockout (DKO) mice improved survival, reduced lung injury, and decreased bacterial load by suppressing NLRP3 + macrophages [2]. In mouse trophoblast stem cells (TSCs), Padi2/3 double knockout led to premature differentiation, altered epigenomic landscape, and reduced DNA methylation at critical trophoblast genes [4]. In prostate cancer, Padi2 was found to promote the progression of castration-resistance prostate cancer (CRPC) by protecting the androgen receptor (AR) against proteasome-mediated degradation [5].

In conclusion, Padi2 plays diverse and crucial roles in biological processes and disease conditions. Studies using KO/CKO mouse models have revealed its significance in cancer, sepsis-induced lung injury, and cell differentiation. Understanding Padi2 through these models provides insights into disease mechanisms and potential therapeutic targets in areas like cancer and inflammatory diseases.

References:

1. Mou, Zezhong, Chen, Yiling, Hu, Jinzhong, Xu, Chenyang, Jiang, Haowen. 2024. Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation. In Acta pharmaceutica Sinica. B, 14, 3916-3930. doi:10.1016/j.apsb.2024.06.029. https://pubmed.ncbi.nlm.nih.gov/39309483/

2. Yu, Xin, Song, Yujing, Dong, Tao, Ma, Jianjie, Li, Yongqing. 2024. Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages. In JCI insight, 9, . doi:10.1172/jci.insight.181686. https://pubmed.ncbi.nlm.nih.gov/39405117/

3. Beato, Miguel, Sharma, Priyanka. 2020. Peptidyl Arginine Deiminase 2 (PADI2)-Mediated Arginine Citrullination Modulates Transcription in Cancer. In International journal of molecular sciences, 21, . doi:10.3390/ijms21041351. https://pubmed.ncbi.nlm.nih.gov/32079300/

4. Ballasy, Noura N, Bering, Elizabeth A, Kokorudz, Caroline, Dean, Wendy, Hemberger, Myriam. 2022. Padi2/3 Deficiency Alters the Epigenomic Landscape and Causes Premature Differentiation of Mouse Trophoblast Stem Cells. In Cells, 11, . doi:10.3390/cells11162466. https://pubmed.ncbi.nlm.nih.gov/36010543/

5. Wang, Lin, Song, Guanhua, Zhang, Xiang, Han, Jinxiang, Han, Bo. 2017. PADI2-Mediated Citrullination Promotes Prostate Cancer Progression. In Cancer research, 77, 5755-5768. doi:10.1158/0008-5472.CAN-17-0150. https://pubmed.ncbi.nlm.nih.gov/28819028/

6. Kim, Hyun-Jung, Shin, Hye-Rim, Yoon, Heein, Choi, Je-Yong, Ryoo, Hyun-Mo. 2023. Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination. In Cell death & disease, 14, 576. doi:10.1038/s41419-023-06101-7. https://pubmed.ncbi.nlm.nih.gov/37648716/