Desferoxamine protects against hemophilic arthropathy through the upregulation of HIF-1α-BNIP3 mediated mitophagy.
Desferoxamine protects against hemophilic arthropathy through the upregulation of HIF-1α-BNIP3 mediated mitophagy.
复制标题
去铁胺通过上调缺氧诱导因子-1α（HIF-1α）-BNIP3介导的线粒体自噬来预防血友病性关节病。
DOI：
10.1016/j.lfs.2022.121172
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发表时间：
2022-11
期刊：
影响因子：
6.1
通讯作者：
Jiamin Lin;Zhou Guo;Zehang Zheng;Liangcai Hou;Jingting Xu;Qiang Liu;Ting Du;Fengjing Guo;Xingzhi Jing
中科院分区：
文献类型：
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作者：
Jiamin Lin;Zhou Guo;Zehang Zheng;Liangcai Hou;Jingting Xu;Qiang Liu;Ting Du;Fengjing Guo;Xingzhi Jing
血友病性关节病（Hemophilic arthropathy，HA）是一种典型的继发于持续性关节出血的铁超载性关节疾病，但铁螯合剂在HA中的确切作用尚未完全阐明。在本研究中，我们调查是否去铁胺（DFO），铁螯合剂，可以限制HA的发展和潜在mechanism.Materials和MethodsA HA小鼠模型建立在FVIII缺陷血友病小鼠左膝穿刺。在DFO给药后8周评价HA进展。此外，软骨细胞用柠檬酸铁铵（FAC）处理，以模拟铁超载在体外。DFO对铁超载引起的氧化应激、软骨细胞凋亡和细胞外基质降解的调节作用以及HIF-1α-BNIP 3介导的线粒体自噬的作用进行了研究。除螯合Fe ~（2+）外，HIF-1α-BNIP 3介导的线粒体自噬在DFO的保护作用中起重要作用。结论：DFO可通过HIF-1α-BNIP 3介导的线粒体自噬抑制HA的形成，提示DFO可能是HA治疗的潜在补充剂。
AimsHemophilic arthropathy (HA) is a typically iron overload induced joint disease secondary to continuous joint bleeding, however, the exact role of iron chelators in HA has not been fully elucidated. In the present study, we investigated whether desferoxamine (DFO), an iron chelator, could limit the development of HA and the underlying mechanisms.Materials and methodsA HA mice model was established by needle puncture in the left knees of FVIII-deficient hemophilic mice. HA progression was evaluated at 8 weeks after DFO administration. Moreover, chondrocytes were treated with ferric ammonium citrate (FAC) to mimic iron overload in vitro. Modulating effect of DFO on iron overload induced oxidative stress, chondrocytes apoptosis and extracellular matrix (ECM) degradation and the role of HIF-1α-BNIP3 mediated mitophagy were examined.Key findingsWe found that DFO limited the development of HA and protected iron overload induced ECM degradation, chondrocytes apoptosis and oxidative stress. Besides chelating Fe2+, we found that HIF-1α-BNIP3 mediated mitophagy played important roles in the protective effect of DFO. HIF-1α inhibition suppressed chondrocytes mitophagy process and partly diminished the protective effect of DFO on chondrocytes iron overload.SignificanceIn conclusion, DFO could protect against HA development via HIF-1α-BNIP3 mediated mitophagy, suggesting DFO might be a potential therapeutic supplement for HA treatment.