Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Binsker, Ulrike; Kohler, Thomas P.; Hammerschmidt, Sven

doi:10.1159/000496033

Cited by 13 publications

(7 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The functions of thrombospondin-1 in immune regulation are complex and are mediated by several thrombospondin-1 receptors (Forslow et al 2007 ; Martin-Manso et al 2008 ; Sarfati et al 2008 ; Stein et al 2016 ; Kaur et al 2021 ). Correspondingly, loss of Thbs1 in mice has been demonstrated to either increase or decrease their survival following exposure to different bacterial, viral, or fungal pathogens (Lawler et al 1998 ; Martin-Manso et al 2012a ; Qu et al 2018 ; Binsker et al 2019 ; Arun et al 2020 ).…”

Section: Insights Into Protective Functions Of Thbs1 In Micementioning

confidence: 99%

Why do humans need thrombospondin-1?

Kaur

Roberts

2023

J. Cell Commun. Signal.

View full text Add to dashboard Cite

Matricellular proteins comprise several families of secreted proteins that function in higher animals at the interface between cells and their surrounding extracellular matrix. Targeted gene disruptions that result in loss of viability in mice have revealed critical roles for several matricellular proteins in murine embryonic development, including two members of the cellular communication network (CCN) gene family. In contrast, mice lacking single or multiple members of the thrombospondin (THBS) gene family remain viable and fertile. The frequency of loss of function mutants, identified using human deep exome sequencing data, provided evidence that some of the essential genes in mice, including Ccn1, are also essential genes in humans. However, a deficit in loss of function mutants in humans indicated that THBS1 is also highly loss-intolerant. In addition to roles in embryonic development or adult reproduction, genes may be loss-intolerant in humans because their function is needed to survive environmental stresses that are encountered between birth and reproduction. Laboratory mice live in a protected environment that lacks the exposures to pathogens and injury that humans routinely face. However, subjecting Thbs1−/− mice to defined stresses has provided valuable insights into functions of thrombospondin-1 that could account for the loss-intolerance of THBS1 in humans. Graphical Abstract

show abstract

Section: Insights Into Protective Functions Of Thbs1 In Micementioning

confidence: 99%

Why do humans need thrombospondin-1?

Kaur

Roberts

2023

J. Cell Commun. Signal.

View full text Add to dashboard Cite

show abstract

“…PECAM1, an endothelial cell adhesion molecule, played a potentially protective role in lung injury and acute respiratory distress syndrome ( 84 , 85 ). THBS1 also has been found to be implicated in the pathogenesis of gram-positive bacteria and the development of lung injury ( 86 , 87 ). For instance, THBS1 loss reduced mouse survival rate, increased lung bacterial burden and lung microvascular permeability, impaired host defense against Pseudomonas aeruginosa ( P. aeruginosa ), and potentiated inflammatory injury during P. aeruginosa acute intrapulmonary infection ( 87 ), while P. aeruginosa is a common pathogen of pneumonia in FMD ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

ITRAQ-based quantitative proteomics analysis of forest musk deer with pneumonia

Tang

Suo²,

Li³

et al. 2022

Front. Vet. Sci.

View full text Add to dashboard Cite

Pneumonia can seriously threaten the life of forest musk deer (FMD, an endangered species). To gain a comprehensive understanding of pneumonia pathogenesis in FMD, iTRAQ-based proteomics analysis was performed in diseased (Pne group) lung tissues of FMD that died of pneumonia and normal lung tissues (Ctrl group) of FMD that died from fighting against each other. Results showed that 355 proteins were differentially expressed (fold change ≥ 1.2 and adjusted P-value < 0.05) in Pne vs. Ctrl. GO/KEGG annotation and enrichment analyses showed that dysregulated proteins might play vital roles in bacterial infection and immunity. Given the close association between bacterial infection and pneumonia, 32 dysregulated proteins related to Staphylococcus aureus infection, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection were screened out. Among these 32 proteins, 13 proteins were mapped to the bovine genome. Given the close phylogenetic relationships of FMD and bovine, the protein-protein interaction networks of the above-mentioned 13 proteins were constructed by the String database. Based on the node degree analysis, 5 potential key proteins related to pneumonia-related bacterial infection in FMD were filtered out. Moreover, 85 dysregulated proteins related to the immune system process were identified given the tight connection between immune dysregulation and pneumonia pathogenesis. Additionally, 12 proteins that might function as crucial players in pneumonia-related immune response in FMD were screened out using the same experimental strategies described above. In conclusion, some vital proteins, biological processes, and pathways in pneumonia development were identified in FMD.

show abstract

“…Studies in mice and primates indicated specific roles for Thbs1 in reproduction (Bender et al 2019; Greenaway et al 2007) and in the ability of adult mice, rats and pigs to repair dermal wounds and survive exposure to ischemic injuries or genotoxic stress (Isenberg et al 2007, 2008a, b; Soto‐Pantoja et al 2015). Loss of Thbs1 in mice also alters their survival following exposure to several pathogens (Arun et al 2020; Binsker et al 2019; Lawler et al 1998; Martin‐Manso et al 2012; Qu et al 2018). Loss of Thbs1 impairs survival for some of these stresses while improving survival or recovery from other stresses.…”

Section: Discussionmentioning

confidence: 99%

Differential intolerance to loss of function and missense mutations in genes that encode human matricellular proteins

Kaur

Roberts

2021

J. Cell Commun. Signal.

View full text Add to dashboard Cite

Targeted gene disruption in mice has provided valuable insights into the functions of matricellular proteins. Apart from missense and loss of function mutations that have been associated with inherited diseases, however, their functions in humans remain unclear. The availability of deep exome sequencing data from over 140,000 individuals in the Genome Aggregation Database provided an opportunity to examine intolerance to loss of function and missense mutations in human matricellular genes. The probability of loss‐of‐function intolerance (pLI) differed widely within members of the thrombospondin, CYR61/CTGF/NOV (CCN), tenascin, small integrin‐binding ligand N‐linked glycoproteins (SIBLING), and secreted protein, acidic and rich in cysteine (SPARC) gene families. Notably, pLI values in humans had limited correlation with viability of the corresponding homozygous null mice. Among the thrombospondins, only THBS1 was highly loss‐intolerant (pLI = 1). In contrast, Thbs1 is not essential for viability in mice. Several known thrombospondin‐1 receptors were similarly loss‐intolerant, although thrombospondin‐1 is not the exclusive ligand for some of these receptors. The frequencies of missense mutations in THBS1 and the gene encoding its signaling receptor CD47 indicated conservation of some residues implicated in specific receptor binding. Deficits in missense mutations were also observed for other thrombospondin genes and for SPARC, SPOCK1, SPOCK2, TNR, and DSPP. The intolerance of THBS1 to loss of function in humans and elevated pLI values for THBS2, SPARC, SPOCK1, TNR, and CCN1 support important functions for these matricellular protein genes in humans, some of which may relate to functions in reproduction or responding to environmental stresses.

show abstract

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

Cited by 13 publications

References 132 publications

Why do humans need thrombospondin-1?

Why do humans need thrombospondin-1?

ITRAQ-based quantitative proteomics analysis of forest musk deer with pneumonia

Differential intolerance to loss of function and missense mutations in genes that encode human matricellular proteins

Contact Info

Product

Resources

About