![]() The mice were sacrificed after feeding for 4 weeks, and the dry lung was weighed. ![]() The mice were injected subcutaneously with 100 μl of PBS or bleomycin and intragastrically with 100 μl of 0.5% CMC-Na or baricitinib once every two days, and the body weight of the mice was simultaneously recorded. After adaptive feeding for 1 week, the mice were randomly divided into 3 groups: the control (PBS + 0.5% CMC-Na, n = 6), bleomycin (7.5 mg/kg bleomycin + 0.5% CMC-Na, n = 13), and baricitinib (7.5 mg/kg bleomycin + 5 mg/kg baricitinib, n = 13) groups. The mice were housed in a room with a temperature of 22–26 ☌ and maintained on a 12 h light–dark cycle with free access to food and water. All animal experiments were reviewed and approved by the Ethics Committee of Chengdu Dashuo Biotechnology Co. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its efficacy and mechanism in SSc-ILD remain unclear.įemale C57BL/6 mice at 6–8 weeks of age were purchased from the Laboratory Animal Centre of Chongqing Medical University (Chongqing, China). Moreover, studies have found that baricitinib shortens recovery time and accelerates symptom improvement in coronavirus disease 2019. Multiple clinical trials and case reports have confirmed that baricitinib can alleviate the clinical symptoms of various diseases, such as psoriasis, atopic dermatitis, and alopecia areata. Nintedanib is the first drug approved by the US Food and Drug Administration for the treatment of SSc-ILD, but more pharmacological treatments are needed to improve the health of patients with SSc-ILD.īaricitinib is a JAK1/2 inhibitor that was approved for the treatment of adults with moderate-to-severe rheumatoid arthritis (RA). Up to 80% of patients with SSc have pulmonary interstitial abnormalities, and the 10-year mortality rate of systemic sclerosis-related interstitial lung disease (SSc-ILD) patients is as high as 40%. The proportion of SSc patients with ILD is as high as 30%. Interstitial lung disease (ILD) is an early complication of SSc and the main cause of death from SSc. Systemic sclerosis (SSc), also known as scleroderma, is an immune-mediated rheumatic disease that is characterized by fibrosis and vascular lesions on the skin and internal organs. Conclusionsīaricitinib attenuated bleomycin-induced skin and lung fibrosis in SSc-ILD mice model by targeting JAK2 and regulating of the crosstalk between the JAK2 and TGF-β1 signaling pathways. Conversely, with successful inhibition of TGF-β receptors in HFLs, JAK2 protein expression decreased. In the vitro experiments, following the culture of HFLs with baricitinib or a STAT3 inhibitor for 48 h, the expression levels of TβRI/II decreased. Baricitinib affected the expression of TGF-β1 and TβRI/II inhibitiing JAK2. The vivo experiments showed that baricitinib notably alleviated skin and lung fibrosis, decreased the concentration of pro-inflammatory factors and increased those of the anti-inflammatory factors. In vitro experiments, we used TGF-β1 and baricitinib to stimulate human fetal lung fibroblasts (HFLs) and assessed protein expression by western blot. We used ELISA, qRT‒PCR, western blot and immunofluorescence staining to evaluate the degree of fibrosis. In vivo experiments, SSc-ILD mice model were constructed by subcutaneous injection of PBS or bleomycin (7.5 mg/kg) and intragastric administration of 0.5% CMC-Na or baricitinib (5 mg/kg) once every two days. We explored crosstalk between the JAK2 and TGF-β1 pathways. The objective of our study was to explore the effect and mechanism of baricitinib in SSc-ILD. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its role in systemic sclerosis-related interstitial lung disease (SSc-ILD) is unclear. Interstitial lung disease is an early complication of SSc and the main cause of death from SSc. ![]() Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis and vascular lesions. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |