Lrrc17-KO Mouse

Lrrc17, leucine-rich repeat containing 17, is involved in multiple biological processes. It is related to pathways like mTOR/PI3K, Wnt, and p53-dependent apoptosis, playing an important role in cell senescence, differentiation, and bone metabolism [1,2,3]. Genetic models are valuable for studying its function.

In bone marrow-derived mesenchymal stem cells (BMSCs), Lrrc17 knockdown activates mitophagy via the mTOR/PI3K pathway, rejuvenates senescent BMSCs, and enhances their therapeutic efficacy in osteoporosis by inhibiting BMSC senescence [1]. In ovarian cancer, knockdown of lrrc17 in zebrafish embryos reduces the survival rate and delays development, indicating its importance in cell viability through the p53-dependent apoptosis pathway [2]. In human bone marrow mesenchymal stem cells from patients with idiopathic necrosis of femoral head, overexpression of LRRC17 promotes osteogenesis and inhibits adipogenesis via the Wnt signaling pathway, while knockout has the opposite effects [3]. In cardiac fibroblasts after myocardial infarction, down-regulation of LRRc17 is associated with increased ferroptosis-related markers and enhanced cell migration and viability, and oe-LRRc17 treatment can reverse these effects [4].

In conclusion, Lrrc17 is crucial in cell-related biological processes and diseases. Its role in BMSC-related bone diseases, ovarian cancer, and myocardial fibrosis has been revealed through gene-knockout or knockdown models. These findings contribute to understanding the mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Liu, Fei, Yuan, Yujia, Bai, Lin, Cheng, Jingqiu, Zhang, Jie. 2021. LRRc17 controls BMSC senescence via mitophagy and inhibits the therapeutic effect of BMSCs on ovariectomy-induced bone loss. In Redox biology, 43, 101963. doi:10.1016/j.redox.2021.101963. https://pubmed.ncbi.nlm.nih.gov/33865167/

2. Oh, Chang-Kyu, Park, Jeong Jun, Ha, Mihyang, Ko, Dai Sik, Kim, Yun Hak. . LRRC17 Is Linked to Prognosis of Ovarian Cancer Through a p53-dependent Anti-apoptotic Function. In Anticancer research, 40, 5601-5609. doi:10.21873/anticanres.14573. https://pubmed.ncbi.nlm.nih.gov/32988884/

3. Song, Da, Wu, Zhen-Song, Xu, Qi, Zhang, Chao, Wang, Da-Wei. 2021. LRRC17 regulates the bone metabolism of human bone marrow mesenchymal stem cells from patients with idiopathic necrosis of femoral head through Wnt signaling pathways: A preliminary report. In Experimental and therapeutic medicine, 22, 666. doi:10.3892/etm.2021.10098. https://pubmed.ncbi.nlm.nih.gov/33986831/

4. Hu, Yao, Peng, Xiaoping. 2024. Single-cell sequencing reveals LRRc17-mediated modulation of cardiac fibroblast ferroptosis in regulating myocardial fibrosis after myocardial infarction. In Cellular signalling, 121, 111293. doi:10.1016/j.cellsig.2024.111293. https://pubmed.ncbi.nlm.nih.gov/38996956/