What question did this study set out to answer?

This research aims to determine the role of syndecan 1 in the progression of acute lung injury (ALI) and its influence on epithelial barrier integrity.

May 20, 2026

B75-03 Syndecan 1, Epithelial Barrier and Fluid Clearance During Acute Lung Injury

Key Points

This research aims to determine the role of syndecan 1 in the progression of acute lung injury (ALI) and its influence on epithelial barrier integrity.
Male and female Sdc1 knockout and wild type mice aged 5-8 weeks were injected with lipopolysaccharide or PBS.
Assessed lung compliance/resistance, alveolar surface area, and conducted bronchoalveolar lavage fluid analysis.
Evaluated lung edema and endothelial permeability through varying assessments, including myeloperoxidase activity and albumin content.
LPS increased lung wet/dry ratio by 1.5-fold in wild type but not in Sdc1 knockout mice.
Sdc1 knockout mice showed increased alveolar surface area and decreased ENaC mRNA compared to wild type mice.
Albumin content in BAL fluid increased due to LPS only in wild type mice.

Abstract

Abstract Rationale Acute lung injury (ALI) is an inflammatory syndrome that may occur secondarily to bacterial infection. Pulmonary edema is a severe complication of ALI and it may result from pulmonary barrier disruption. The mechanisms that initiate ALI during bacterial infection remains unresolved. Syndecan 1 (Sdc1) is a heparan sulfate proteoglycan that contributes to barrier stability and is cleaved during inflammatory processes. Whether Sdc1 contributes to ALI progression is unresolved. Herein we investigated if Sdc1 mediates LPS-induced ALI in mice. Methods Male and Female Sdc1 knockout (Sdc1KO) and wild type (WT) mice, with 5-8 weeks of age, were injected with lipopolysaccharide (LPS, 10mg/Kg, IP) or PBS and euthanized after 6hr. Lung compliance/resistance was assessed with the Flexivent system. Alveolar surface area was determined using the MLI methodology. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected and assessed for myeloperoxidase (MPO) activity, albumin content, and expression of ENaC, Aquaporin 5, CFTR and surfactants (A-D). Lung edema was assessed by lung wet/dry ratio (W/D), lung endothelial permeability was assessed by Evans Blue extravasation. Results and Conclusions LPS increased lung W/D by 1.5-fold and Evans blue extravasation by 1 fold in WT but not Sdc1KO mice. Sdc1KO showed higher basal lung W/D vs WT, increased alveolar surface area, but similar Evans blue extravasation indices. Similarly, a trend increase in basal lung MPO activity was seen in Sdc1KO when compared to WT. A significant increase in MPO activity was seen in both LPS-treated WT and LPS-treated Sdc1KO mice when compared to matched PBS-treated strain controls. Albumin content was increased by LPS only in WT BAL. Sdc1KO showed decreased ENaC mRNA in lung homogenates vs. WT mice. Collectively, our data suggests that Sdc1KO shows basal lung epithelial barrier failure. This phenotype is associated with decreased response to LPS. The mechanisms whereby Sdc1 regulate barrier function may involve decreased fluid filtration via ENaC-dependent pathways. Sdc1 may participate in lung edema progression during ALI. This abstract is funded by: None

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