Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influxOAMEDLINE
To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.
Ziqian Xiang;Pengfei Zhang;Chunwang Jia;Rongkun Xu;Dingren Cao;Zhaoning Xu;Tingting Lu;Jingwei Liu;Xiaoxiong Wang;Cheng Qiu;Wenyang Fu;Weiwei Li;Lei Cheng;Qiang Yang;Shiqing Feng;Lianlei Wang;Yunpeng Zhao;Xinyu Liu;
Department of Orthopaedics,Qilu Hospital of Shandong University,Jinan 250012,China University of Health and Rehabilitation Sciences,Qingdao 226000,ChinaDepartment of Orthopaedics,Qilu Hospital of Shandong University,Jinan 250012,ChinaXiangya School of Medicine,Central South University,Changsha 410013,ChinaSchool of Nursing and Rehabilitation,Shandong University,Jinan 250012,ChinaDepartment of Pediatrics,Cangzhou Central Hospital,Cangzhou 061011,ChinaDepartment of Pediatric Surgery,Qilu Hospital of Shandong University,Jinan 250012,ChinaDepartment of Pathology,Qilu Hospital of Shandong University,Jinan 250012,ChinaDepartment of Spine Surgery,Tianjin Hospital,Tianjin University,Tianjin 30021,ChinaDepartment of Orthopaedics,Qilu Hospital of Shandong University,Jinan 250012,China The Second Hospital of Shandong University,Cheeloo College of Medicine,Shandong University,Jinan 250012,China
基础医学
stressoverloadchannel
《Bone Research》 2024 (002)
P.334-348 / 15
supported in part by the National Nature Science Foundation(81874022 and 82172483 to Xinyu Liu,82102522 to Lianlei Wang,82072478 to Yunpeng Zhao,82072435 to Qiang Yang,82073437 to Weiwei Li,81930070 to Shiqing Feng,82272548 to Lei Cheng);Key R&D Project of Shandong Province(2022CXGC010503 to Xinyu Liu);Shandong Natural Science Foundation(ZR202102210113 to Lianlei Wang,ZR2020YQ54 to Yunpeng Zhao);Shandong Province Taishan Scholar Project(tsqn202211317 to Lianlei Wang).The authors thank the Translational Medicine Core Facility of Shandong University for the consultation and instrument availability that supported this work.
评论