文章标题：Micelle encapsulation zinc-doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair
影响因子：7.4
期刊：Bioengineering & Translational Medicine
作者列表：Jingyan Yi, Xin Luo, Jinshan Xing, Aharon Gedanken, Xiukun Lin, Chunxiang Zhang, Gan Qiao
发表时间：2023-3-28
DOI:10.1002/btm2.10507
主要研究成果：Hematopoietic stem cells (HSCs) possess great self-renewal and multidirectional differentiation abilities, which contribute to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, the precise regulation of hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using an MC5R knockout mouse model, we observed that it is not essential for steady-state hematopoiesis. Interestingly, the levels of α-melanocyte stimulating hormone (α-MSH), an important subtype of melanocortin, were elevated in the serum and bone marrow, and the expression of MC5R was upregulated in HSPCs from mice after irradiation. MC5R deficiency aggravates irradiation-induced myelosuppression because of impaired proliferation and reconstitution of HSCs. Further investigation revealed that the melanocortin/MC5R axis regulates the proliferation of HSCs by activating the PI3K/AKT and MAPK pathways. More importantly, α-MSH treatment can significantly accelerate hematopoietic recovery in irradiated mice. In conclusion, our data demonstrate that the melanocortin/MC5R axis plays a crucial role in regulating HSC proliferation under stress, thus providing a promising strategy to promote hematopoietic regeneration when suffering from injury.
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论文网址：https://aiche.onlinelibrary.wiley.com/doi/full/10.1002/btm2.10507
