Pim1, short for proviral integration site for Moloney murine leukemia virus-1, is a serine/threonine protein kinase. It is involved in numerous biological events such as cell survival, cycle progression, proliferation, and migration. Pim1 participates in multiple signaling pathways including Wnt, Notch, AKT/FOXO1, NRF2/HO-1/NQO1, and NF-κB, and is of great biological importance in immunoregulation and oncogenesis [3,4]. Genetic models like KO/CKO mouse models are valuable for studying its functions.

In colitis and colitis-associated colorectal cancer (CAC), epithelial Pim1 in mice leads to decreased goblet cells, impairing resistance. Pim1 modulates goblet cell differentiation via the Wnt and Notch signaling pathways, and interacts with HDAC2, downregulating its level through phosphorylation [1]. In uveitis, inhibiting Pim1 in experimental autoimmune uveitis (EAU) mouse models reduces Th17 cell proportion, increases Treg cell proportion, and decreases Th17 cell pathogenicity and plasma cell differentiation [2]. In cisplatin-induced acute kidney injury (AKI), Pim1 inhibition in mice aggravates the injury, while overexpression attenuates it by inhibiting Drp1 activation [5].

In conclusion, Pim1 plays essential roles in maintaining intestinal homeostasis, immune regulation, and kidney protection as revealed through mouse model-based research. Its dysregulation is associated with diseases like colitis, CAC, uveitis, and cisplatin-induced AKI. Studies on Pim1 using KO/CKO mouse models contribute to understanding the disease mechanisms and potentially developing new therapeutic strategies for these diseases.

References:

1. Yang, Jianming, Xiao, Yawen, Zhao, Ningning, Yao, Zhi, Wang, Quan. 2024. PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification. In Acta pharmaceutica Sinica. B, 14, 3049-3067. doi:10.1016/j.apsb.2024.04.017. https://pubmed.ncbi.nlm.nih.gov/39027246/

2. Li, He, Xie, Lihui, Zhu, Lei, Zheng, Yingfeng, Su, Wenru. 2022. Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis. In Nature communications, 13, 5866. doi:10.1038/s41467-022-33502-7. https://pubmed.ncbi.nlm.nih.gov/36195600/

3. Yang, Xue, Liu, Chunming, Lei, Yuxi, Zhu, Bin, Zhao, Dongchi. 2024. PIM1 signaling in immunoinflammatory diseases: an emerging therapeutic target. In Frontiers in immunology, 15, 1443784. doi:10.3389/fimmu.2024.1443784. https://pubmed.ncbi.nlm.nih.gov/39372407/

4. Choudhury, Rituparna, Bahadi, Chandan Kumar, Ray, Ipsa Pratibimbita, Patnaik, Srinivas, Nikhil, Kumar. 2024. PIM1 kinase and its diverse substrate in solid tumors. In Cell communication and signaling : CCS, 22, 529. doi:10.1186/s12964-024-01898-y. https://pubmed.ncbi.nlm.nih.gov/39487435/

5. Li, Yuzhen, Shi, Lang, Zhao, Fan, Wu, Xiongfei, Zhu, Jiefu. 2023. PIM1 attenuates cisplatin-induced AKI by inhibiting Drp1 activation. In Cellular signalling, 113, 110969. doi:10.1016/j.cellsig.2023.110969. https://pubmed.ncbi.nlm.nih.gov/37967691/