Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 3;22(11):3640-3651.
doi: 10.1021/acs.jproteome.3c00576. Epub 2023 Oct 18.

Plasma TNFRSF11B as a New Predictive Inflammatory Marker of Sepsis-ARDS with Endothelial Dysfunction

Dong Zhang  1 , Changjuan Xu  2 , Jintao Zhang  2 , Rong Zeng  1 , Qian Qi  2 , Jiawei Xu  2 , Yun Pan  1 , Xiaofei Liu  2 , Shuochuan Shi  2 , Jianning Zhang  2 , Liang Dong  1   2
Affiliations

Plasma TNFRSF11B as a New Predictive Inflammatory Marker of Sepsis-ARDS with Endothelial Dysfunction

Dong Zhang et al. J Proteome Res. .

Abstract

Inflammation plays an important role in the development of sepsis-acute respiratory distress syndrome (ARDS). Olink inflammation-related biomarker panels were used to analyze the levels of 92 inflammation-related proteins in plasma with sepsis-ARDS (n = 25) and healthy subjects (n = 25). There were significant differences in 64 inflammatory factors, including TNFRSF11B in sepsis-ARDS, which was significantly higher than that in controls. Functional analysis showed that TNFRSF11B was closely focused on signal transduction, immune response, and inflammatory response. The TNFRSF11B level in sepsis-ARDS plasma, LPS-induced mice, and LPS-stimulated HUVECs significantly increased. The highest plasma concentration of TNFRSF11B in patients with sepsis-ARDS was 10-20 ng/mL, and 10 ng/mL was selected to stimulate HUVECs. Western blot results demonstrated that the levels of syndecan-1, claudin-5, VE-cadherin, occludin, aquaporin-1, and caveolin-1 in TNFRSF11B-stimulated HUVECs decreased, whereas that of connexin-43 increased in TNFRSF11B-stimulated HUVECs. To the best of the authors' knowledge, this study was the first to reveal elevated TNFRSF11B in sepsis-ARDS associated with vascular endothelial dysfunction. In summary, TNFRSF11B may be a new potential predictive and diagnostic biomarker for vascular endothelium damage in sepsis-ARDS.

Keywords: TNFRSF11B; endothelial dysfunction; glycocalyx; junctions; sepsis−ARDS.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
All DEPs in inflammation-related biomarkers between the sepsis–ARDS and control groups. (A) Protein expression in the sepsis–ARDS (n = 25) and control groups (n = 25). (B) Volcanic visualization of DEPs based on 92 inflammation-related biomarkers, including OPG (TNFRSF11B) in sepsis–ARDS, was significantly higher than that in controls. (C) Heatmap of 92 inflammation-related proteins.
Figure 2
Figure 2
GO and KEGG enrichment analyses of DEPs. (A) GO enrichment analysis with a scatter plot based on the background of 92 inflammation-related proteins. (B) KEGG enrichment analysis with a scatter plot based on the background of 92 inflammation-related proteins. (C) GO enrichment analysis with a bar plot based on the background of 92 inflammation-related proteins. (D) KEGG enrichment bar plot analysis with a bar plot based on the background of 92 inflammation-related proteins.
Figure 3
Figure 3
(A) Correlative analysis between DEPs in sepsis–ARDS and control groups. (B) Visualization of the correlation between OPG (TNFRSF11B) and DEPs. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. NS, not significant.
Figure 4
Figure 4
(A) PPI network analysis between TNFRSF11B and CCL2, FGF23, TNFSF10, and IL7. (B) Visualization of the PPI network analysis of DEPs.
Figure 5
Figure 5
Validation of TNFRSF11B in human sepsis–ARDS serum, LPS-induced mice, and LPS-stimulated HUVECs. (A) Olink data visualization of TNFRSF11B. (B) Receiver operating characteristic (ROC) curve of serum TNFRSF11B in sepsis–ARDS and control groups. (C) Validation of TNFRSF11B concentration in sepsis–ARDS and control groups. (D) ROC curve of TNFRSF11B concentration in sepsis–ARDS and control groups. (E) Lung injury was evaluated by HE staining. (F) mRNA level of TNFRSF11B in LPS-induced ARDS mice. (G) mRNA level of TNFRSF11B in LPS-stimulated HUVECs. (H) Protein level of TNFRSF11B in LPS-induced ARDS mice. (I) Protein level of TNFRSF11B in LPS-stimulated HUVECs. (J) TNFRSF11B intensity in LPS-induced ARDS mice. (K) TNFRSF11B intensity in LPS-stimulated HUVECs. (L) TNFRSF11B concentration of serum in LPS-induced ARDS mice. (M) TNFRSF11B concentration of cell culture medium in LPS-stimulated HUVECs. Data are expressed as the means ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. NS, not significant.
Figure 6
Figure 6
Validation of the TNFRSF11B function in HUVECs. (A) Western blot detection of occludin, claudin-5, VE-cadherin, SDC-1, Cav-1, and AQP-1, CX-43, and ZO-1 proteins. (B) Relative protein intensity in TNFRSF11B-stimulated HUVECs. Data are expressed as the means ± SD of three independent experiments. *p < 0.05, **p < 0.01. NS, not significant.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Identification of a multi-omics factor predictive of long COVID in the IMPACC study.
    Gabernet G, Maciuch J, Gygi JP, Moore JF, Hoch A, Syphurs C, Chu T, Jayavelu ND, Corry DB, Kheradmand F, Baden LR, Sekaly RP, McComsey GA, Haddad EK, Cairns CB, Rouphael N, Fernandez-Sesma A, Simon V, Metcalf JP, Agudelo Higuita NI, Hough CL, Messer WB, Davis MM, Nadeau KC, Pulendran B, Kraft M, Bime C, Reed EF, Schaenman J, Erle DJ, Calfee CS, Atkinson MA, Brackenridge SC, Melamed E, Shaw AC, Hafler DA, Ozonoff A, Bosinger SE, Eckalbar W, Maecker HT, Kim-Schulze S, Steen H, Krammer F, Westendorf K; IMPACC Network; Peters B, Fourati S, Altman MC, Levy O, Smolen KK, Montgomery RR, Diray-Arce J, Kleinstein SH, Guan L, Ehrlich LIR. Gabernet G, et al. bioRxiv [Preprint]. 2025 Feb 14:2025.02.12.637926. doi: 10.1101/2025.02.12.637926. bioRxiv. 2025. PMID: 39990442 Free PMC article. Preprint.
  • The glycocalyx: a key target for treatment of severe acute pancreatitis-associated multiple organ dysfunction syndrome.
    Li H, Wen H, Liu J, Luo X, Pei B, Ge P, Sun Z, Liu J, Wang J, Chen H. Li H, et al. Hum Cell. 2025 May 24;38(4):107. doi: 10.1007/s13577-025-01227-6. Hum Cell. 2025. PMID: 40411704 Free PMC article. Review.
  • Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.
    Li K, Feng J, Li M, Han L, Wu Y. Li K, et al. Mediators Inflamm. 2025 Feb 12;2025:2003124. doi: 10.1155/mi/2003124. eCollection 2025. Mediators Inflamm. 2025. PMID: 39974277 Free PMC article.
  • TNFSF11/TNFRSF11A Axis Amplifies HDM-Induced Airway Remodeling by Strengthening TGFβ1/STAT3 Action.
    Zhang D, Zhang J, Qi Q, Pan Y, Zeng R, Xu C, Liu X, Xu J, Gao M, Gao T, Zhang J, Shi S, Dong L. Zhang D, et al. Allergy Asthma Immunol Res. 2024 Jul;16(4):399-421. doi: 10.4168/aair.2024.16.4.399. Allergy Asthma Immunol Res. 2024. PMID: 39155739 Free PMC article.
  • Baseline predictors for 28-day COVID-19 severity and mortality among hospitalized patients: results from the IMPACC study.
    Hou J, Haslund-Gourley B, Diray-Arce J, Hoch A, Rouphael N, Becker PM, Augustine AD, Ozonoff A, Guan L, Kleinstein SH, Peters B, Reed E, Altman M, Langelier CR, Maecker H, Kim S, Montgomery RR, Krammer F, Wilson M, Eckalbar W, Bosinger SE, Levy O, Steen H, Rosen LB, Baden LR, Melamed E, Ehrlich LIR, McComsey GA, Sekaly RP, Schaenman J, Shaw AC, Hafler DA, Corry DB, Kheradmand F, Atkinson MA, Brakenridge SC, Agudelo Higuita NI, Metcalf JP, Hough CL, Messer WB, Pulendran B, Nadeau KC, Davis MM, Fernandez Sesma A, Simon V, Kraft M, Bime C, Calfee CS, Erle DJ, Impacc Network, Robinson LF, Cairns CB, Haddad EK, Comunale MA. Hou J, et al. Front Med (Lausanne). 2025 Jul 4;12:1604388. doi: 10.3389/fmed.2025.1604388. eCollection 2025. Front Med (Lausanne). 2025. PMID: 40687705 Free PMC article.
See all "Cited by" articles

References

    1. Zhou Y.; Li P.; Goodwin A. J.; Cook J. A.; Halushka P. V.; Chang E.; et al. Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury. Crit. Care 2019, 23 (1), 4410.1186/s13054-019-2339-3. - DOI - PMC - PubMed
    1. Caudrillier A.; Kessenbrock K.; Gilliss B. M.; Nguyen J. X.; Marques M. B.; Monestier M.; et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J. Clin. Invest. 2012, 122 (7), 2661–2671. 10.1172/JCI61303. - DOI - PMC - PubMed
    1. Simmons S.; Erfinanda L.; Bartz C.; Kuebler W. M. Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation. J. Physiol. 2019, 597 (4), 997–1021. 10.1113/JP276245. - DOI - PMC - PubMed
    1. LaRivière W. B.; Schmidt E. P.. The pulmonary endothelial glycocalyx in ARDS: a critical role for heparan sulfate. In Current Topics in Membranes; Elsevier, 2018; Vol. 82, pp 33–52. - PubMed
    1. Wautier J. L.; Wautier M. P. Vascular permeability in diseases. Int. J. Mol. Sci. 2022, 23 (7), 364510.3390/ijms23073645. - DOI - PMC - PubMed

Publication types