BMC cardiovascular disorders · 2025
Baricitinib represses the myocardial fibrosis via blocking JAK/STAT and TGF-β1 pathways in vivo and in vitro.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Feng Renlei, Liu Hongli, Chen Yunqing
Аннотация
BACKGROUND: JAK/STAT pathway is closely involved in the organ fibrotic process. The current study aimed to investigate the impact of baricitinib, an oral selective JAK1/JAK2 inhibitor, on the myocardial fibrosis in vivo and the activation of cardiac fibroblasts in vitro.
METHODS: The mouse myocardial fibrosis model was established by isoproterenol (ISO) treatment, then was treated by baricitinib. The activation of mouse cardiac fibroblasts was established by TGF-β1 stimulation, then was treated by baricitinib with several concentrations. Besides, JAK2 was knocked down by small interfering RNA (siRNA) in TGF-β1-stimulated mouse cardiac fibroblasts.
RESULTS: Baricitinib not only attenuated myocardial cell widening, inflammatory infiltration, fibrous tissue, and heart index, but also reduced collagen volume fraction, the expressions of Col1, Col3, α-SMA, Fn, MMP9, and TIMP1 in ISO-induced myocardial fibrosis mice. Meanwhile, baricitinib decreased the expressions of p-STAT3 and TGF-βRII in these mice. Interestingly, in TGF-β1-stimulated cardiac fibroblasts, baricitinib decreased the expressions of Col1, Col3, α-SMA, Fn, MMP9, and TIMP1 in a dose-dependent manner (From 10 to 2000 nM), also exhibited a dose-dependent impact on the expressions of p-STAT3 and TGF-βRII. Finally, JAK2 knockdown by siRNA downregulated the expressions of Col1, Col3, α-SMA, and Fn in TGF-β1-stimulated cardiac fibroblasts.
CONCLUSION: Inhibition of JAK/STAT pathway by baricitinib represses the myocardial fibrosis in vivo and in vitro, indicating baricitinib may be a treatment option for myocardial fibrosis, while further validation is needed.
METHODS: The mouse myocardial fibrosis model was established by isoproterenol (ISO) treatment, then was treated by baricitinib. The activation of mouse cardiac fibroblasts was established by TGF-β1 stimulation, then was treated by baricitinib with several concentrations. Besides, JAK2 was knocked down by small interfering RNA (siRNA) in TGF-β1-stimulated mouse cardiac fibroblasts.
RESULTS: Baricitinib not only attenuated myocardial cell widening, inflammatory infiltration, fibrous tissue, and heart index, but also reduced collagen volume fraction, the expressions of Col1, Col3, α-SMA, Fn, MMP9, and TIMP1 in ISO-induced myocardial fibrosis mice. Meanwhile, baricitinib decreased the expressions of p-STAT3 and TGF-βRII in these mice. Interestingly, in TGF-β1-stimulated cardiac fibroblasts, baricitinib decreased the expressions of Col1, Col3, α-SMA, Fn, MMP9, and TIMP1 in a dose-dependent manner (From 10 to 2000 nM), also exhibited a dose-dependent impact on the expressions of p-STAT3 and TGF-βRII. Finally, JAK2 knockdown by siRNA downregulated the expressions of Col1, Col3, α-SMA, and Fn in TGF-β1-stimulated cardiac fibroblasts.
CONCLUSION: Inhibition of JAK/STAT pathway by baricitinib represses the myocardial fibrosis in vivo and in vitro, indicating baricitinib may be a treatment option for myocardial fibrosis, while further validation is needed.