The anti-scar effect of tyrosine-kinase inhibitor nintedanib in experimental glaucoma filtration surgery in rabbits

Yüksel, Refref; Yüksel, Nurşen; Yazır, Yusufhan; Öztürk, Ahmet; Rençber, Selenay Furat; Küçük, Kübra Demirci

doi:10.1016/j.exer.2023.109431

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Nintedanib has been extensively investigated in the pathological fibrosis of lung tissue 32–34 and has also been reported in extrapulmonary tissues, such as repair after urethral injury, 35 scar formation after glaucoma surgery, 36 and pulmonary sarcoidosis combined with rheumatoid arthritis 37 . A recent report showed that nintedanib antagonizes pathological CHON‐001 chondrocyte injury in vitro 23 .…”

Section: Discussionmentioning

confidence: 99%

Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by M1 polarization of synovial macrophages via the MAPK/PI3K‐AKT pathway

Yan,

Feng,

Yang

et al. 2023

The FASEB Journal

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Synovial inflammation and fibrosis are important pathological changes associated with osteoarthritis (OA). Herein, we investigated if nintedanib, a drug specific for pulmonary fibrosis, plays a positive role in osteoarthritic synovial inflammation and fibrosis. We assessed the effect of nintedanib on osteoarthritic synovial inflammation and fibrosis in a mouse model of OA created by destabilization of the medial meniscus and a macrophage M1 polarization model created by stimulating RAW264.7 cells with lipopolysaccharide. Histological staining showed that daily gavage administration of nintedanib significantly alleviated articular cartilage degeneration, reduced the OARSI score, upregulated matrix metalloproteinase‐13 and downregulated collagen II expression, and significantly reduced the synovial score and synovial fibrosis in a mouse OA model. In addition, immunofluorescence staining showed that nintedanib significantly decreased the number of M1 macrophages in the synovium of a mouse model of OA. In vitro results showed that nintedanib downregulated the phosphorylation levels of ERK, JNK, p38, PI3K, and AKT while inhibiting the expression of macrophage M1 polarization marker proteins (CD86, CD80, and iNOS). In conclusion, this study suggests that nintedanib is a potential candidate for OA treatment. The mechanisms of action of nintedanib include the inhibition of M1 polarization in OA synovial macrophages via the MAPK/PI3K‐AKT pathway, inhibition of synovial inflammation and fibrosis, and reduction of articular cartilage degeneration.

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