HIF-1α inhibition attenuates severity of Achilles tendinopathy by blocking NF-κB and MAPK pathways

• Published in: International immunopharmacology 2022-05, Vol.106, p.108543-108543, Article 108543
• Main Authors: Jiao, Xin, Zhang, Yuxin, Li, Wentao, Zhou, Xianhao, Chu, Wenxiang, Li, Yiming, Wang, Zengguang, Sun, Xin, Xu, Chen, Gan, Yaokai
• Format: Article
• Language: English
• Subjects: Achilles Tendon; Athletes; Cell proliferation; Extracellular signal-regulated kinase; HIF-1α; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Inflammation; Inhibition; Kinases; MAP kinase; MAP Kinase Signaling System; MAPK; Migration; NF-kappa B - metabolism; NF-κB; NF-κB protein; Phosphorylation; Proliferation; Quality of life; Signal Transduction; Signaling; Tendinopathy; Tendinopathy - drug therapy
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108543

•HIF-1α is highly expressed in tendinopathy.•YC-1 is an effective and potential HIF-1α inhibitor to treat tendinopathy.•HIF-1α inhibition decreases migration and proliferation of tendon cells under inflammation environment.•HIF-1α inhibition alleviates inflammation of tendon cells via NF-κB and MAPK pathways. Tendinopathy is a common disease influencing life quality and tendon function of patients, especially in the elderly and athletes. Inflammation is an important pathologic process of tendinopathy. Hypoxia inducible factor-1 alpha (HIF-1α) participates actively in inflammatory process. However, little is known about the role of HIF-1α in tendinopathy. To address this issue, we verified the expression level of HIF-1α in tendinopathy in vivo and in vitro. Furthermore, the severity of tendinopathy in vivo and in vitro was assessed after HIF-1α inhibition. At the same time, inflammatory signaling cascades were evaluated. The expression level of HIF-1α increased in tendinopathy in vivo and in vitro. The migration and proliferation of tendon cells (TDCs) were reduced after HIF-1α inhibition. In the meantime, HIF-1α inhibition alleviated the severity of tendinopathy and promoted tendon repairing. We also found that HIF-1α inhibition reduced the phosphorylation levels of p65 in NF-κB signaling pathway and the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and Jun N-terminal kinase (JNK) in MAPK signaling pathway. These findings suggest that HIF-1α increases in tendinopathy in vivo and vitro, and HIF-1α inhibition can suppress the severity of tendinopathy by blocking NF-κB and MAPK signaling pathways.