The concentration-dependent pro-fibrotic effect of metformin on LPS and high glucose induced fibroblast NIH 3T3 and macrophage raw 264.7 cell co-culture

Introduction: Diabetes mellitus is known as one of the risk factors for Idiopathic Pulmonary Fibrosis (IPF) development. Recently, metformin, the commonly used antidiabetic medication, is reported to have a therapeutic effect in IPF. However, the benefit of metformin therapy in IPF is still controversial. The study aims to investigate the metformin effect on the fibroblast and macrophage co-culture under lipopolysaccharides (LPS) and high glucose treatment. Method: The NIH 3T3 and RAW 264.7 co-culture were induced with LPS and high glucose before it was treated with metformin in different concentration. After 24 hours of treatment, the media and the cells were collected for further examination. The collagen expression was measured using Sirius red dye in the media. The IL-6 and TGF β mRNA examination were done using real-time PCR. Result: Our study showed that NIH 3T3 and RAW 264.7 co-culture treated with metformin has higher collagen expression, but lower IL-6 mRNA expression compares to those on co-culture without treatment. Conclusion: Metformin increases fibrosis markers in LPS and high glucose-induced NIH 3T3 and RAW 264.7 co-culture despite its ability to improve IL-6 mRNA expression. © 2020 Elsevier B.V., All rights reserved.