Cryab-KO Mouse

CRYAB, also known as α -Crystallin B, is a member of the small heat shock protein family. It is involved in various cellular processes such as apoptosis, inflammation, and oxidative stress signaling pathways. Initially discovered in the eye lens, it is associated with multiple diseases including eye and heart diseases, as well as cancers like breast, lung, prostate, and ovarian cancer [1].

In osteoporosis, the mRNA level of CRYAB was decreased in patients' plasma. Overexpression of CRYAB promoted osteogenic differentiation of human bone marrow stem cells (BMSCs), while knockdown had opposite effects. Mechanistically, CRYAB interacted with and stabilized ferritin heavy chain 1 (FTH1), suppressing ferroptosis in BMSCs [2]. In colorectal cancer (CRC), CRYAB expression was elevated in tumor tissues. Knockdown of CRYAB induced ferroptosis in CRC cells by preventing β -catenin from interacting with TRIM55, increasing β -catenin protein stability and accelerating cancer progression [3]. In cardiomyocytes, overexpression of CRYAB increased heat resistance, likely by reducing F -actin aggregation, regulating the cell cycle, and preventing caspase-mediated apoptosis [4]. In myocardial ischemia-reperfusion (I/R) injury, the activation of LBH-CRYAB signaling alleviated apoptosis and ferroptosis of cardiomyocytes, with p53 as a downstream effector [5]. In CRC, CRYAB maintained cancer stem cell (CSC) formation via the Wnt/β-catenin pathway, enhancing CSC-related properties [6].

In summary, CRYAB plays crucial roles in multiple biological processes and diseases. Its functions in promoting osteogenic differentiation, affecting cancer progression, protecting cardiomyocytes under stress, and in I/R injury are revealed through various functional studies. These findings from different research models help in understanding the essential biological functions of CRYAB and may provide potential therapeutic targets for related diseases.

References:

1. Zhang, JunFei, Liu, Jia, Wu, JiaLi, Chen, ZhongWei, Yang, LiShan. 2019. Progression of the role of CRYAB in signaling pathways and cancers. In OncoTargets and therapy, 12, 4129-4139. doi:10.2147/OTT.S201799. https://pubmed.ncbi.nlm.nih.gov/31239701/

2. Tian, Bo, Li, Xiaolu, Li, Weiyuan, Wan, Ping, Zhu, Chongtao. 2024. CRYAB suppresses ferroptosis and promotes osteogenic differentiation of human bone marrow stem cells via binding and stabilizing FTH1. In Aging, 16, 8965-8979. doi:10.18632/aging.205851. https://pubmed.ncbi.nlm.nih.gov/38787373/

3. Xia, Haiyan, Chen, Jingwen, Zhang, Wenbo, Nai, Yongjun, Wei, Xiaowei. 2024. CRYAB Promotes Colorectal Cancer Progression by Inhibiting Ferroptosis Through Blocking TRIM55-Mediated β-Catenin Ubiquitination and Degradation. In Digestive diseases and sciences, 69, 3799-3809. doi:10.1007/s10620-024-08584-6. https://pubmed.ncbi.nlm.nih.gov/39126452/

4. Yin, Bin, Tang, Shu, Xu, Jiao, Li, Yubao, Bao, Endong. 2018. CRYAB protects cardiomyocytes against heat stress by preventing caspase-mediated apoptosis and reducing F-actin aggregation. In Cell stress & chaperones, 24, 59-68. doi:10.1007/s12192-018-0941-y. https://pubmed.ncbi.nlm.nih.gov/30246229/

5. Wu, Anbiao, Zhong, Chongbin, Song, Xudong, Yang, Pingzhen, Liu, Qicai. 2024. The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis. In iScience, 27, 109510. doi:10.1016/j.isci.2024.109510. https://pubmed.ncbi.nlm.nih.gov/38660406/

6. Dai, Ang, Guo, Xiaohong, Yang, Xiaoqing, Fu, Yanxin, Sun, Qing. . Effects of the CRYAB gene on stem cell-like properties of colorectal cancer and its mechanism. In Journal of cancer research and therapeutics, 18, 1328-1337. doi:10.4103/jcrt.jcrt_212_22. https://pubmed.ncbi.nlm.nih.gov/36204880/