Abstract

Background: Acute respiratory distress syndrome (ARDS) contributes to increased global mortality in ARDS patients due to dysfunctional alveolar epithelial type II (AT2) cells. However, the role of doublecortin-like kinase 1 (DCLK1) in AT2 cells remains unclear in ARDS. Therefore, the objective of this study is to investigate the DCLK1 expression in AT2 cells with ARDS.

Methods: Male C57BL/6 mice were intratracheally (i.t.) administered 7.5 mg/kg of lipopolysaccharide (LPS) to induce ARDS, followed by collecting bronchoalveolar lavage fluid (BALF) and lung samples on days 3 and 7. Mice that received phosphate-buffered saline (PBS) under the same protocol served as control. The mouse lungs were fixed in 10% neutral buffered formalin for lung injury score evaluation, and the TUNEL assay was conducted to determine apoptotic cells in the lungs of mice.

Results: Our results showed increasing levels of total protein, lactate dehydrogenase (LDH) and tumor necrosis factor (TNF)-? in BALF of ARDS mice. A significant increase in lung injury score and apoptotic bodies by TUNEL assay were found in ARDS mouse lungs within 7 days. Notably, we observed a significant reduction of DCLK1 expression in surfactant protein C-positive (SPC+) cells on day 3 and subsequently increased expression on SPC+ cells during 7 days in ARDS mice.

Conclusions: Our results showed that DCLK1 was dynamically expressed on AT2 cells in different stages of ARDS pathogenesis, which could be involved in the underlying mechanisms of ARDS.