Increased progranulin as an independent predictive biomarker for poor prognosis in sepsis

Shan, Yi; Zhang, Xiaoli; Zhou, Guanghui; Ji, XiuHai; Yi, Zili

doi:10.1016/j.cyto.2022.155911

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…These high CCL2 concentrations may be a reactive process to sepsis-mediated failure to contain bacterial infection that does not achieve full protection. Similar observations have been made for other mediators, such as progranulin (31,59), which can promote protection against bacterial clearance in sepsis. The positive relationship between high concentrations of CCL2 and septic death in our analysis of the prognostic value of CCL2 concentrations is consistent with this scenario.…”

Section: Discussionsupporting

confidence: 77%

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

Bai,

Lu,

et al. 2024

Sci. Transl. Med.

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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–β 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.

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Section: Discussionsupporting

confidence: 77%

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

Bai,

Lu,

et al. 2024

Sci. Transl. Med.

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“…GRN , at elevated levels, has been associated with poor prognosis in infectious diseases. Serum GRN levels in sepsis exhibited positively correlation with inflammatory factors including hypersensitive C-reactive protein and procalcitonin [ 55 ]. The cell counts of neutrophils and macrophages were increased in transcutaneous puncture wounds under administration of GRN [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential biological processes and key genes in diabetes-related stroke through weighted gene co-expression network analysis

He,

Bai,

Huang

et al. 2024

BMC Med Genomics

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Background Type 2 diabetes mellitus (T2DM) is an established risk factor for acute ischemic stroke (AIS). Although there are reports on the correlation of diabetes and stroke, data on its pathogenesis is limited. This study aimed to explore the underlying biological mechanisms and promising intervention targets of diabetes-related stroke. Methods Diabetes-related datasets (GSE38642 and GSE44035) and stroke-related datasets (GSE16561 and GSE22255) were obtained from the Gene Expression omnibus (GEO) database. The key modules for stroke and diabetes were identified by weight gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses were employed in the key module. Genes in stroke- and diabetes-related key modules were intersected to obtain common genes for T2DM-related stroke. In order to discover the key genes in T2DM-related stroke, the Cytoscape and protein–protein interaction (PPI) network were constructed. The key genes were functionally annotated in the Reactome database. Results By intersecting the diabetes- and stroke-related crucial modules, 24 common genes for T2DM-related stroke were identified. Metascape showed that neutrophil extracellular trap formation was primarily enriched. The hub gene was granulin precursor (GRN), which had the highest connectivity among the common genes. In addition, functional enrichment analysis indicated that GRN was involved in neutrophil degranulation, thus regulating neutrophil extracellular trap formation. Conclusions This study firstly revealed that neutrophil extracellular trap formation may represent the common biological processes of diabetes and stroke, and GRN may be potential intervention targets for T2DM-related stroke.

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Type-I interferon shapes peritoneal immunity in cirrhosis and drives caspase-5-mediated progranulin release upon infection

Rooney,

Duduskar,

Ghait

et al. 2024

Journal of Hepatology

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Increased progranulin as an independent predictive biomarker for poor prognosis in sepsis

Cited by 4 publications

References 36 publications

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

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

Identification of potential biological processes and key genes in diabetes-related stroke through weighted gene co-expression network analysis

Type-I interferon shapes peritoneal immunity in cirrhosis and drives caspase-5-mediated progranulin release upon infection

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