Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant

Müller, Hanna; End, Caroline; Renner, Marcus; Helmke, Burkhard; Gaßler, Nikolaus; Weiß, Christel; Hartl, Dominik; Griese, Matthias; Hafner, Mathias; Poustka, Annemarie; Mollenhauer, Jan; Poeschl, Johannes

doi:10.1186/1465-9921-8-69

Cited by 12 publications

(22 citation statements)

References 39 publications

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“…Indeed, high levels of DMBT1/gp340/SAG were found in the tracheal aspirates and lung tissue sections of newborn infants with bacterial infections (Mü ller et al, 2007) and in the A549 lung cell line after pro-inflammatory stimulation with PMA (Kang et al, 2002). Inflammation-whether induced by TNF␣, by LPS, or by inflammatory bowel disease-also up-regulated DMBT1/gp340/SAG expression in intestinal epithelial cells Rosenstiel et al, 2007).…”

Section: A Role In Epithelial Cell Differentiation and Pathogen Recomentioning

confidence: 99%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Martínez

Moestrup²,

Holmskov

et al. 2011

Pharmacological Reviews

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164

155

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Section: A Role In Epithelial Cell Differentiation and Pathogen Recomentioning

confidence: 99%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Martínez

Moestrup²,

Holmskov

et al. 2011

Pharmacological Reviews

Self Cite

164

155

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“…The DMBT1 expression in these hypoxic lungs is significantly higher than expected in these gestational ages as demonstrated (Figure 1 C,F) and already described by our research group. 5,6 3.2 | DMBT1 expression in A549 cells after normoxia and hypoxia…”

Section: Dmbt1 Expression In Lung Tissue After Fetal/ Peri-/postnatmentioning

confidence: 99%

“…Earlier studies demonstrated that hrDMBT1 is able to inactivate the function of surfactant preparations widely used to treat respiratory distress syndrome. 5 In this study we analyzed the effect of hrDMBT1 on the surfactant ultrastructure as the morphology of surfactant is closely related to its function. 11 Lamellar body-like forms are regarded as surface-active precursors from which the active surface layer is generated.…”

Section: Influence Of Human Recombinant Dmbt1 (Hrdmbt1) On Surfactamentioning

confidence: 99%

“…In addition, recent studies indicated that lung epithelial cells of preterm and term infants showed expression of the protein Deleted in Malignant Brain Tumors 1 (DMBT1). 5,6 DMBT1 has functions in innate immunity and is upregulated in the lungs of neonates with bacterial infections and inflammation.…”

mentioning

confidence: 99%

“…Further, DMBT1 is present in hyaline membranes during respiratory distress syndrome and inactivates surfactant preparations characterized by increasing surface tension of surfactant preparations in a dosedependent manner. 5,6 The aim of the present study was to evaluate whether DMBT1 seems to be a link between hypoxia and surfactant inactivation, because both hypoxia and DMBT1 impair surfactant function.…”

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confidence: 99%

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DMBT1 is upregulated in lung epithelial cells after hypoxia and changes surfactant ultrastructure

Müller

Schmiedl

Weiß

et al. 2020

Pediatric Pulmonology

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Background: Hypoxia and asphyxia are known to induce surfactant inactivation in newborns. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. It was detected in hyaline membranes of infants with respiratory distress syndrome. Human recombinant DMBT1 is able to increase the surface tension of exogenous surfactant preparations in a dose-dependent manner. Methods: Immunohistochemistry was performed on lung sections of infants who died due to pre-, peri-or postnatal hypoxia. The lung epithelial cell line A549 was stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty plasmid (DMBT1− cells). The cells were cultured in normoxic or hypoxic conditions, and then DMBT1 as well as HIF-1α RNA expression were analyzed by using real-time-polymerase chain reaction. Human recombinant DMBT1 was added to the modified porcine natural surfactant Curosurf to examine the effect of DMBT1 on surfactant ultrastructure with electron microscopy. Results: DMBT1 expression was upregulated in human lung tissue after fetal/peri-/ postnatal hypoxia. In addition, in vitro experiments showed increased DMBT1 RNA expression in A549 cells after hypoxia. HIF-1α was upregulated in both DMBT1+ and DMBT1− cells in response to hypoxia. The addition of human recombinant DMBT1 to Curosurf caused an impaired surfactant ultrastructure. Conclusions: DMBT1 is upregulated in response to hypoxia and there seems to be a link between hypoxia and surfactant inactivation.

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Elevated DMBT1 levels in neonatal gastrointestinal diseases

Müller

Renner

Helmke

et al. 2015

Histochem Cell Biol

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Deleted in malignant brain tumor 1 (DMBT1) is involved in innate immunity and epithelial differentiation. Previous studies in adults indicated a strong intestinal expression of DMBT1 and an important role in inflammatory bowel diseases. Here, we analyzed the DMBT1 expression in the fetal gastrointestinal system depending on gestational age and in patients with necrotizing enterocolitis (NEC), volvulus, intestinal perforation (IP), or herniation, representing typical diseases of preterm and term infants. We used immunohistochemistry and RNA in situ hybridization to detect DMBT1 protein and mRNA in fetal tissues, supplemented by postmortem analysis of DMBT1 expression in died newborns and analysis of surgically removed tissues. DMBT1 expression is detectable in the early developmental stages of the gastrointestinal system. In NEC, volvulus, IP, or herniation, characterized by high systemic inflammatory responses, DMBT1 expression is strongly increased. High DMBT1 expression was also found in the bile ducts of older infants with sepsis or cholestasis. The study shows that DMBT1 expression is observed in the developing gastrointestinal system and up-regulated in infants with NEC, volvulus, IP, and herniation. DMBT1 may play a role in epithelial differentiation and local innate immunity during neonatal inflammatory bowel processes.

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Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant

Cited by 12 publications

References 39 publications

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

DMBT1 is upregulated in lung epithelial cells after hypoxia and changes surfactant ultrastructure

Elevated DMBT1 levels in neonatal gastrointestinal diseases

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