Ankrd1, also known as ankyrin repeat domain 1, has a dual function in the cytoplasm as part of the I-band of the sarcomere and in the nucleus as a transcriptional cofactor. It is involved in multiple biological pathways, including Wnt/β-catenin, NF-κB-MAGE-A6, and FAK/Rho-GTPase/F-actin, and is important in processes like cell differentiation, senescence, and tissue repair [2,3,5,6]. Genetic models are valuable for studying its role in various biological processes and diseases.

In renal ischaemia-reperfusion injury (IRI), global knockdown of Ankrd1 in mouse kidney cells by rAAV9 mitigated ischaemia/reperfusion-induced renal damage and failure. In vitro, silencing Ankrd1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells [1]. In ovariectomized mice, silencing Ankrd1 in bone marrow-derived mesenchymal stem cells (BMSCs) impaired osteogenesis and Wnt/β-catenin signaling activation [3]. In neonatal mice, Ankrd1 knockdown in cardiomyocytes inhibited myocardial regeneration after apical resection, while cardiomyocyte-specific overexpression in adult mice promoted cardiac repair after myocardial infarction [4]. In C2C12 myoblasts, Ankrd1 knockdown led to decreased proliferation but increased differentiation by activating the FAK/Rho-GTPase/F-actin pathway [5].

In conclusion, Ankrd1 is a key regulator in multiple biological processes. Findings from gene knockout or knockdown mouse models have revealed its significance in diseases such as renal IRI, osteoporosis, and ischemic heart disease, suggesting it could be a potential therapeutic target in these disease areas.

References:

1. Han, Shangting, Guo, Jiayu, Kong, Chenyang, Cheng, Fan, Zhou, Jiangqiao. . ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25-mediated ubiquitination of ACSL3. In Clinical and translational medicine, 14, e70024. doi:10.1002/ctm2.70024. https://pubmed.ncbi.nlm.nih.gov/39285846/

2. Xie, Rong, Yuan, Shuai, Hu, Guo, Wang, Dao Wen, Li, Huaping. 2024. Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 1578-1594. doi:10.1016/j.ymthe.2024.03.018. https://pubmed.ncbi.nlm.nih.gov/38475992/

3. Zhang, Yiqi, Zhou, Long, Fu, Qin, Liu, Ziyun. 2023. ANKRD1 activates the Wnt signaling pathway by modulating CAV3 expression and thus promotes BMSC osteogenic differentiation and bone formation in ovariectomized mice. In Biochimica et biophysica acta. Molecular basis of disease, 1869, 166693. doi:10.1016/j.bbadis.2023.166693. https://pubmed.ncbi.nlm.nih.gov/36958710/

4. Liu, Liu, Jiang, Qiqi, Du, Chong, Wang, Hao, Wang, Liansheng. 2024. Ankrd1 regulates endogenous cardiac regeneration in mice by modulating cyclin D1. In European journal of pharmacology, 983, 177005. doi:10.1016/j.ejphar.2024.177005. https://pubmed.ncbi.nlm.nih.gov/39299480/

5. Huang, Cheng, Zhong, Qiqi, Lian, Weisi, Hu, Jinling, Lei, Minggang. 2024. Ankrd1 inhibits the FAK/Rho-GTPase/F-actin pathway by downregulating ITGA6 transcriptional to regulate myoblast functions. In Journal of cellular physiology, 239, e31359. doi:10.1002/jcp.31359. https://pubmed.ncbi.nlm.nih.gov/38988048/

6. Diskul-Na-Ayudthaya, Penchatr, Bae, Seon Joo, Bae, Yun-Ui, Kim, Wootae, Ryu, Seongho. 2024. ANKRD1 Promotes Breast Cancer Metastasis by Activating NF-κB-MAGE-A6 Pathway. In Cancers, 16, . doi:10.3390/cancers16193306. https://pubmed.ncbi.nlm.nih.gov/39409926/