Bone morphogenetic protein 9 is a candidate prognostic biomarker and host-directed therapy target for sepsis

作者全名："Bai, Haobo; Lu, Qian; Wu, Chunxiang; Xu, Fang; Liu, Jiayu; Wang, Ke; Ding, Hao; Yin, Yibing; Liu, Yi; Lai, Xiaofei; Cao, Ju"

作者地址："[Bai, Haobo; Lu, Qian; Wang, Ke; Ding, Hao; Lai, Xiaofei; Cao, Ju] Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing 400016, Peoples R China; [Lu, Qian] Chongqing Med Univ, Biol Sci Inst, Chongqing 400016, Peoples R China; [Wu, Chunxiang] Sichuan Acad Med Sci, Dept Clin Lab Med, Chengdu 610072, Peoples R China; [Wu, Chunxiang] Sichuan Prov Peoples Hosp, Chengdu 610072, Peoples R China; [Xu, Fang] Chongqing Med Univ, Dept Crit Care Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Liu, Jiayu; Yin, Yibing] Chongqing Med Univ, Sch Lab Med, Key Lab Lab Med Diagnost Designated, Minist Educ, Chongqing 400016, Peoples R China; [Liu, Yi] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA"

通信作者："Lai, XF; Cao, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing 400016, Peoples R China."

来源：SCIENCE TRANSLATIONAL MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001186131000006

JCR分区：Q1

影响因子：17.1

年份：2024

卷号：16

期号：732

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Defining next-generation immune therapeutics for the treatment of sepsis will involve biomarker-based therapeutic decision-making. Bone morphogenetic protein 9 (BMP9) is a cytokine in the transforming growth factor-beta superfamily. Here, circulating BMP9 concentrations were quantified in two independent cohorts of patients with sepsis. Decreased concentrations of serum BMP9 were observed in the patients with sepsis at the time of admission as compared with healthy controls. Concentrations of BMP9 at the time of admission were also associated with 28-day mortality, because patients with sepsis at a higher risk of death had lower BMP9 concentrations. The mechanism driving the contribution of BMP9 to host immunity was further investigated using in vivo murine sepsis models and in vitro cell models. We found that BMP9 treatment improved outcome in mice with experimental sepsis. BMP9-treated mice exhibited increased macrophage influx into the peritoneal cavity and more efficient bacterial clearance than untreated mice. In vitro, BMP9 promoted macrophage recruitment, phagocytosis, and subsequent bacterial killing. We further found that deletion of the type 1 BMP receptor ALK1 in macrophages abolished BMP9-mediated protection against polymicrobial sepsis in vivo. Further experiments indicated that the regulation of macrophage activation by the BMP9-ALK1 axis was mainly mediated through the suppressor of mother against decapentaplegic 1/5 signaling pathway. Together, these results suggest that BMP9 can both serve as a biomarker for patient stratification with an independent prognostic value and be developed as a host-directed therapy for sepsis."

基金机构："National Natural Science Foundation of China [82070014, 82370009]; Natural Science Foundation Project of Chongqing [CSTB2022NSCQ- lZX0017]; Sichuan Science and Technology Program [2022YFS0238]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJZD- K201900405]"

基金资助正文："This work was supported by grants from National Natural Science Foundation of China (grant nos. 82070014 and 82370009 to J.C.), Natural Science Foundation Project of Chongqing (grant no. CSTB2022NSCQ- lZX0017 to J.C.), Sichuan Science and Technology Program (grant no. 2022YFS0238 to C.W.), and Scientific and Technological Research Program of Chongqing Municipal Education Commission (grant no. KJZD- K201900405 to J.C.)"