Angelica sinensis polysaccharides prevents hematopoietic regression in D-Galactose-Induced aging model via attenuation of oxidative stress in hematopoietic microenvironment

作者全名："Jing, Pengwei; Song, Xiaoying; Xiong, Lirong; Wang, Biyao; Wang, Yaping; Wang, Lu"

作者地址："[Jing, Pengwei; Song, Xiaoying; Xiong, Lirong; Wang, Biyao; Wang, Yaping; Wang, Lu] Chongqing Med Univ, Lab Stem Cells & Tissue Engn, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Song, Xiaoying] Peoples Hosp Jiajiang, Leshan 614100, Peoples R China; [Wang, Yaping; Wang, Lu] Chongqing Med Univ, Dept Histol & Embryol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Wang, L (通讯作者)，Chongqing Med Univ, Lab Stem Cells & Tissue Engn, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Wang, L (通讯作者)，Chongqing Med Univ, Dept Histol & Embryol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000876852100005

JCR分区：Q3

影响因子：2.8

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Angelica sinensis polysaccharide; Bone marrow stroma; Hematopoietic stem; progenitor cell; Oxidative stress; Stress-induced premature senescence

摘要："Background Extrinsic molecular mechanisms that regulate hematopoietic stem/progenitor cell (HSPC) aging are still poorly understood, and a potential protective medication needs to be explored. Materials and methods The senescent parameters of hematopoietic cells and bone marrow stromal cells (BMSCs) including cell cycle analysis, senescence-associated SA-beta-gal staining and signals, hematopoietic factors and cellular junction were analyzed in femur and tibia of rats. Furthermore, Sca-1(+) HSPCs and BMSCs co-culture system was established to evaluate the direct effects of BMSC feeder layer to HSPCs. Oxidative DNA damage indicators in Sca-1(+) HSCs and senescence-associated secretory phenotype (SASP) of BMSCs, gap junction intercellular communication between BMSCs, osteogenesis/adipogenisis differentiation balance of BMSCs were detected. Results In the D-gal pre-administrated rats, ASP treatment rescued senescence of hematopoietic cells and BMSCs, reserved CFU-GEMM; also, ASP treatment attenuated stromal oxidative load, ameliorated SCF, CXCL12, and GM-CSF production, increased Connexin-43 (Cx43) expression. BMSCs and Sca-1(+) HSPCs co-cultivation demonstrated that ASP treatment prevented oxidative DNA damage response in co-cultured Sca-1(+) HSPCs induced by D-gal pre-administration of feeder layer and the underlying mechanism may be related to ASP ameliorating feeder layer dysfunction due to D-gal induced senescence via inhibiting secretion of IL-1, IL-6, TNF-alpha, and RANTES, enhancing Cx43-mediated intercellular communication, improving Runx2 expression whereas decreasing PPAR gamma expression in BMSCs. Conclusion The antioxidant property of ASP may provide a stroma-mediated potential therapeutic strategy for HSPC aging."

基金机构："National Natural Science Foundation of China [81873103]; Basic and frontier research project of Chongqing Science and Technology Commission [cstc2014jcyjA10001, cstc2021jcyj-msxmX0669]"

基金资助正文："This research was funded by the National Natural Science Foundation of China (No. 81873103) and the grant from Basic and frontier research project of Chongqing Science and Technology Commission (cstc2014jcyjA10001, cstc2021jcyj-msxmX0669)."