Meprin and ADAM proteases as triggers of systemic inflammation in sepsis

Rahn, Sascha; Becker‐Pauly, Christoph

doi:10.1002/1873-3468.14225

Cited by 11 publications

(15 citation statements)

References 242 publications

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“…This is the case of the repression of the ADAM proteins which belong to the matrix‐metalloproteinases family. They allow the detachment of adhesion proteins which play a central role in attracting inflammatory cells to sites of tissue damage and regulate the activation and phagocytic activity of immune cells (Rahn & Becker‐Pauly, 2022 ). Some ADAM genes might have a protective role against some parasites (Geurts et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic resource for aquaculture

Boutet

Monteiro

Baudry

et al. 2022

Evolutionary Applications

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The European flat oyster (Ostrea edulis L.) is a native bivalve of the European coasts. Harvest of this species has declined during the last decades because of the appearance of two parasites that have led to the collapse of the stocks and the loss of the natural oyster beds. O. edulis has been the subject of numerous studies in population genetics and on the detection of the parasites Bonamia ostreae and Marteilia refringens. These studies investigated immune responses to these parasites at the molecular and cellular levels. Several genetic improvement programs have been initiated especially for parasite resistance. Within the framework of a European project (PERLE 2) that aims to produce genetic lines of O. edulis with hardiness traits (growth, survival, resistance) for the purpose of repopulating natural oyster beds in Brittany and reviving the culture of this species in the foreshore, obtaining a reference genome becomes essential as done recently in many bivalve species of aquaculture interest. Here, we present a chromosome‐level genome assembly and annotation for the European flat oyster, generated by combining PacBio, Illumina, 10X linked, and Hi‐C sequencing. The finished assembly is 887.2 Mb with a scaffold‐N50 of 97.1 Mb scaffolded on the expected 10 pseudochromosomes. Annotation of the genome revealed the presence of 35,962 protein‐coding genes. We analyzed in detail the transposable element (TE) diversity in the flat oyster genome, highlighted some specificities in tRNA and miRNA composition, and provided the first insight into the molecular response of O. edulis to M. refringens. This genome provides a reference for genomic studies on O. edulis to better understand its basic physiology and as a useful resource for genetic breeding in support of aquaculture and natural reef restoration.

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Section: Discussionmentioning

confidence: 99%

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic resource for aquaculture

Boutet

Monteiro

Baudry

et al. 2022

Evolutionary Applications

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“…Exosomes represent a platform for cellular communication and signaling in the human body. Based on the stability of exosomes in the blood system [55], P. aeruginosa triggered release of exosomes upon local infection in the lung could result in systemic effects either through spreading of the shedding products (inflammatory and pro-inflammatory mediators) or transporting the proteases to other tissues to mediate the proteolytic activity [56].…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Triggered Exosomal Release of ADAM10 Mediates Proteolytic Cleavage in Trans

Aljohmani

Opitz

Bischoff

et al. 2022

IJMS

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Pneumonia is a life-threatening disease often caused by infection with Streptococcus pneumoniae and Pseudomonas aeruginosa. Many of the mediators (e.g., TNF, IL-6R) and junction molecules (e.g., E-cadherin) orchestrating inflammatory cell recruitment and loss of barrier integrity are proteolytically cleaved through a disintegrin and metalloproteinases (ADAMs). We could show by Western blot, surface expression analysis and measurement of proteolytic activity in cell-based assays, that ADAM10 in epithelial cells is upregulated and activated upon infection with Pseudomonas aeruginosa and Exotoxin A (ExoA), but not upon infection with Streptococcus pneumoniae. Targeting ADAM10 by pharmacological inhibition or gene silencing, we demonstrated that this activation was critical for cleavage of E-cadherin and modulated permeability and epithelial integrity. Stimulation with heat-inactivated bacteria revealed that the activation was based on the toxin repertoire rather than the interaction with the bacterial particle itself. Furthermore, calcium imaging experiments showed that the ExoA action was based on the induction of calcium influx. Investigating the extracellular vesicles and their proteolytic activity, we could show that Pseudomonas aeruginosa triggered exosomal release of ADAM10 and proteolytic cleavage in trans. This newly described mechanism could constitute an essential mechanism causing systemic inflammation in patients suffering from Pseudomonas aeruginosa-induced pneumonia stimulating future translational studies.

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“…Inflammation plays a central role in the progression of AKI (Han et al, 2020 ; Vázquez‐Carballo et al, 2021 ) and kidney injury induced by IR (Meng et al, 2020 ). In AKI, IL‐6 signaling is a key link for local and systemic inflammation (Joseph et al, 2020 ; Rahn & Becker‐Pauly, 2021 ; Shang et al, 2020 ). In the IL‐6 “classic signaling pathway” a pro‐inflammatory pathway, the epithelial cells membrane‐bound IL‐6 receptor (mbIL‐6R) binds to gp130 receptor to activate a downstream signaling cascade (Ebihara et al, 2011 ; Grigoryev et al, 2008 ; Malchow et al, 2011 ; Rose‐John & Heinrich, 1994 ; Scheller et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Meprin β expression modulates the interleukin‐6 mediated JAK2‐STAT3 signaling pathway in ischemia/reperfusion‐induced kidney injury

Abousaad

Ahmed

Abouzeid

et al. 2022

Physiological Reports

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Meprin metalloproteinases have been implicated in the pathophysiology of ischemia/reperfusion (IR)‐induced kidney injury. Previous in vitro data showed that meprin β proteolytically processes interleukin‐6 (IL‐6) resulting in its inactivation. Recently, meprin‐β was also shown to cleave the IL‐6 receptor. The goal of this study was to determine how meprin β expression impacts IL‐6 and downstream modulators of the JAK2‐STAT3‐mediated signaling pathway in IR‐induced kidney injury. IR was induced in 12‐week‐old male wild‐type (WT) and meprin β knockout (βKO) mice and kidneys obtained at 24 h post‐IR. Real‐time PCR, western blot, and immunostaining/microscopy approaches were used to quantify mRNA and protein levels respectively, and immunofluorescence counterstaining with proximal tubule (PT) markers to determine protein localization. The mRNA levels for IL‐6, CASP3 and BCL‐2 increased significantly in both genotypes. Interestingly, western blot data showed increases in protein levels for IL‐6, CASP3, and BCL‐2 in the βKO but not in WT kidneys. However, immunohistochemical data showed increases in IL‐6, CASP3, and BCL‐2 proteins in select kidney tubules in both genotypes, shown to be PTs by immunofluorescence counterstaining. IR‐induced increases in p‐STAT‐3 and p‐JAK‐2 in βKO at a global level but immunoflourescence counterstaining demonstrated p‐JAK2 and p‐STAT3 increases in select PT for both genotypes. BCL‐2 increased only in the renal corpuscle of WT kidneys, suggesting a role for meprins expressed in leukocytes. Immunohistochemical analysis confirmed higher levels of leukocyte infiltration in WT kidneys when compared to βKO kidneys. The present data demonstrate that meprin β modulates IR‐induced kidney injury in part via IL‐6/JAK2/STAT3‐mediated signaling.

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Meprin and ADAM proteases as triggers of systemic inflammation in sepsis

Cited by 11 publications

References 242 publications

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic resource for aquaculture

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic resource for aquaculture

Pseudomonas aeruginosa Triggered Exosomal Release of ADAM10 Mediates Proteolytic Cleavage in Trans

Meprin β expression modulates the interleukin‐6 mediated JAK2‐STAT3 signaling pathway in ischemia/reperfusion‐induced kidney injury

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