Pharmacological Inhibition of STING/TBK1 Signaling Attenuates Myeloid Fibroblast Activation and Macrophage to Myofibroblast Transition in Renal Fibrosis

• DOI: 10.3389/fphar.2022.940716
• Publication Date: 2022-07-18T08:21:40Z
• Authors: Haimei Zeng; Ying Gao; Wenqiang Yu; Jiping Liu; Chaoqun Zhong; Xi Su; Shihong Wen; Hua Liang
• Keywords: Myofibroblast; Sting

Renal fibrosis is an important pathological biomarker of chronic kidney disease (CKD). Stimulator interferon genes/TANK binding kinase 1 (STING/TBK1) axis has been identified as the main regulator innate immune response and closely related to fibrotic disorder. However, role STING/TBK1 signaling pathway in still unknown. In this study, we investigated effect pharmacological inhibition on renal induced by folic acid (FA). mice, TBK1 was significantly activated interstitial cells FA-injured kidneys, which markedly inhibited H-151 (a STING inhibitor) treatment. Specifically, impaired bone marrow-derived fibroblasts activation macrophage myofibroblast transition nephropathy, leading reduction extracellular matrix proteins expression, myofibroblasts formation development fibrosis. Furthermore, GSK8612 reduced myeloid accumulation impeded differentiation, resulting less deposition protein severe lesion kidneys. cultured mouse monocytes, TGF-β1 signaling. This abolished or inhibitor administration. addition, treatment decreased levels α-smooth muscle actin prevents macrophages vitro . Collectively, our results revealed that a critical fibroblast activation, transition, progression.