LPS-induced monocarboxylate transporter-1 inhibition facilitates lactate accumulation triggering epithelial-mesenchymal transformation and pulmonary fibrosis

• DOI: 10.1007/s00018-024-05242-y
• Publication Date: 2024-05-06T06:02:28Z
• Authors: Jinhua Feng; Han Zhong; Shuya Mei; Ri Tang; Yang Zhou; Shunpeng Xing; Yuan Gao; Qiaoyi Xu; Zhengyu He
• Keywords: Monocarboxylate transporter

Abstract The epithelial-mesenchymal transformation (EMT) process of alveolar epithelial cells is recognized as involved in the development pulmonary fibrosis. Recent evidence has shown that lipopolysaccharide (LPS)-induced aerobic glycolysis lung tissue and elevated lactate concentration are associated with pathogenesis sepsis-associated However, it uncertain whether LPS promotes fibrosis by promoting accumulation tissue, thereby initiating EMT process. We hypothesized monocarboxylate transporter-1 (MCT1), main protein for transport, may be crucial pathogenic found high concentrations induced while moderate did not. Besides, we demonstrated MCT1 inhibition enhanced MLE-12 cells, upregulation could reverse lactate-induced EMT. promote through accumulation, this alleviated upregulating expression MCT1. In addition, overexpression prevented LPS-induced vivo. Altogether, study revealed inhibit mouse cause transport disorder, which leads to ultimately