<i>LCMR1</i> deficiency exacerbates LPS‑induced lung injury in lung‑on‑a‑chip and mouse models

The oncogene lung cancer metastasis‑related protein 1 (<i>LCMR1</i>) is associated with neoplastic diseases and <i>LCMR1</i> conditional knockout affects cell homeostasis. In the present study, the role of <i>LCMR1</i> in lipopolysaccharide (LPS)‑induced acute lung injury (ALI) was investigated. Firstly, wild‑type C57BL/6 mice were used to establish an LPS‑induced ALI model via intratracheal injection of LPS, and the expression of <i>LCMR1</i> was examined at 24, 48, 72 and 96 h after injury. The LPS‑induced lung injury model was subsequently constructed in mice with conditional knockout of LCMR1 in type II alveolar epithelial cells (AEC‑II). Subsequently, histopathological analysis, lung wet/dry weight ratio comparisons and lung function tests were performed; survival rates after LPS challenge of the conditional knockout mice were measured; bronchoalveolar lavage fluid (BALF) was collected, and the concentrations of protein and inflammatory cytokines in BALF were measured; and transmission electron microscopy of lung tissue was conducted to evaluate the degree of lung injury. To further investigate the mechanism, a lung‑on‑a‑chip model with overexpression or knockdown of <i>LCMR1</i> was constructed to simulate the alveolar environment under LPS treatment. The expression levels of E‑cadherin and pro‑pulmonary surfactant C precursor (proSP‑C) in the chips were determined by immunofluorescence, and the integrity of the air‑blood barrier was analyzed using a permeability assay. In the mouse model, LCMR1 expression was downregulated in wild‑type mice with LPS‑induced lung injury. <i>LCMR1</i> conditional knockout in AEC‑II caused increased mortality, impaired lung function, aggravated pathological damage and increased the inflammatory response in mice with LPS‑induced ALI. Furthermore, in the lung‑on‑a‑chip model, <i>LCMR1</i> knockdown reduced the expression of E‑cadherin and proSP‑C, and impaired the air‑blood barrier function, whereas <i>LCMR1</i> overexpression attenuated these effects, which may be related to cell differentiation dysfunction and enhanced apoptosis. In conclusion, the present study revealed that <i>LCMR1</i> deficiency may exacerbate LPS‑induced ALI and could be considered a novel target for intervention in ALI.