ANKRD22, ankyrin repeat domain 22, is a nuclear-encoded mitochondrial membrane protein. It is highly expressed in normal gastric mucosal epithelial cells and activated macrophages. As a regulator of mitochondrial Ca2+, it is involved in the Wnt/β-catenin pathway, playing a significant role in repairing damaged gastric mucosa [1]. It also has functions related to inflammation resolution and immune regulation, thus being of great biological importance. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

ANKRD22-deficient mice show more susceptibility to IMQ-induced psoriasiform inflammation, as ANKRD22 deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in hyperproduction of IL-23 in DCs [2]. In ovarian cancer, knockout of Ankrd22 in mouse CD11b+Ly6G+Ly6Clow cells increases the expression level of CCR2 and the immunosuppressive activity of PMN-MDSCs, promoting the proliferation of ovarian cancer cells in tumor xenograft mouse models [3]. In septic ARDS model mice, knockdown of ANKRD22 significantly attenuates acute lung injury and reduces the M1 polarization of lung macrophages [4]. In gliomas, loss of ANKRD22 suppresses glioma cell proliferation, migration, invasion and cell cycle progression in vitro and tumor growth in vivo [5]. In papillary thyroid carcinoma, knockdown of ANKRD22 reduces cell viability, colony formation, invasion and migration abilities, and impairs the activation of the Wnt/β-catenin signaling pathway [6].

In conclusion, ANKRD22 is crucial in multiple biological processes including tissue repair, inflammation resolution, and immune regulation. Research using KO/CKO mouse models has revealed its roles in various disease conditions such as psoriasis, ovarian cancer, septic ARDS, gliomas, and papillary thyroid carcinoma. These findings suggest that ANKRD22 could be a potential therapeutic target for these diseases.

References:

1. Wang, Rui, Wu, Youhe, Zhu, Yue, Yao, Sheng, Zhu, Yongliang. 2022. ANKRD22 is a novel therapeutic target for gastric mucosal injury. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 147, 112649. doi:10.1016/j.biopha.2022.112649. https://pubmed.ncbi.nlm.nih.gov/35051858/

2. Xia, Xichun, Zhu, Leqing, Xu, Miaomiao, Huang, Fang, Gao, Yunfei. 2024. ANKRD22 promotes resolution of psoriasiform skin inflammation by antagonizing NIK-mediated IL-23 production. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 1561-1577. doi:10.1016/j.ymthe.2024.03.007. https://pubmed.ncbi.nlm.nih.gov/38454607/

3. Chen, Huanhuan, Yang, Keqing, Pang, Lingxiao, Zhu, Yongliang, Zhou, Jianwei. . ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs in ovarian cancer. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2022-005527. https://pubmed.ncbi.nlm.nih.gov/36822671/

4. Zhang, Shi, Liu, Yao, Zhang, Xiao-Long, Sun, Yun, Lu, Zhong-Hua. 2023. ANKRD22 aggravates sepsis-induced ARDS and promotes pulmonary M1 macrophage polarization. In Journal of translational autoimmunity, 8, 100228. doi:10.1016/j.jtauto.2023.100228. https://pubmed.ncbi.nlm.nih.gov/38225946/

5. Liu, Xin, Zhao, Junling, Wu, Qiang, Lu, Wenpeng, Feng, Yan. . ANKRD22 promotes glioma proliferation, migration, invasion, and epithelial-mesenchymal transition by upregulating E2F1-mediated MELK expression. In Journal of neuropathology and experimental neurology, 82, 631-640. doi:10.1093/jnen/nlad034. https://pubmed.ncbi.nlm.nih.gov/37164633/

6. Wu, Yange, Chen, WenXiu, Zhang, Bo, Liu, HongXia. 2023. ANKRD22 knockdown suppresses papillary thyroid cell carcinoma growth and migration and modulates the Wnt/β-catenin signaling pathway. In Tissue & cell, 84, 102193. doi:10.1016/j.tice.2023.102193. https://pubmed.ncbi.nlm.nih.gov/37586180/