DOI: 10.1002/ame2.12320
Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice
Yuhang Sun
Bowen Guan
Xing Liu
Lingyan Zhang
Xinpei Wang
Aimin Meng
Ran Gao
National Human Diseases Animal Model Resource Center,NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC),National Center of Technology Innovation for Animal Model,Beijing,China
摘要：Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-induced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for pos-sible biomarkers based on differences in protein expression abundance was validated using enzyme-linked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and an-giogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase path-ways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC suscep-tibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-induced HSC injury.Using GD mice to construct genetic differ-ence models will provide preclinical data for screening BU-related biological markers.
机标关键词：screeningstemcellmicebusulfandiversegeneticallyhematopoietic
论文发表日期：2023-04-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 146-154 )
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