Journal
MOLECULAR IMMUNOLOGY
Volume 150, Issue -, Pages 29-38Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2022.07.007
Keywords
Frozen shoulder; Fibrosis; Fibroblasts; Interleukin 6; PI3K-Akt signaling pathway
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Funding
- National Natural Science Foun-dation of China [81972067]
- Guangzhou Science and Technology Program Key projects [201704020132]
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This study explored the role of IL-6 and the PI3K-Akt signaling pathway in the fibrotic process in synovial fibroblasts of frozen shoulder (FS). The findings indicate that IL-6 is up-regulated in FS synovial fibroblasts and promotes fibrosis through the PI3K-Akt signaling pathway.
Fibrosis is the main cause of limited range of motion (ROM) of shoulder in patients with frozen shoulder (FS). Overexpression of Interleukin 6 (IL-6) has been correlated with pathogenesis of FS. However, the underlying mechanism remains largely unexplored. In the current study, we focused on isolating synovial fibroblasts of FS and determining the influence of IL-6 as well as PI3K-Akt signaling pathway on the fibrotic process of synovial fibroblasts in FS by using RNA Sequencing (RNA-seq) and other molecular biology techniques. Synovial fibro-blasts of FS express more extra cellular matrix (ECM) than that of control. RNA-seq results and bioinformatic analysis indicate that PI3K-Akt signaling pathway play an important role in the fibrotic process of FS, and IL-6 is the most related gene among those related to this process. The expression levels of IL-6 / IL-6R in FS synovial fibroblasts and IL-6 in culture supernatant were both significantly increased. siRNA interference with the expression of IL-6 attenuates the fibrosis level of FS as well as phosphorylation level of Akt. The findings suggest that synovial fibroblasts are key effector cells of fibrosis of FS. Activation of PI3K-Akt pathway can promote fibrosis of synovial fibroblasts in FS. IL-6 is up-regulated in synovial fibroblasts of FS and promoted the FS fibrosis through PI3K-Akt signaling pathway.
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