Almost every life form,from the tiniest bacterium to humans,is mechanosensitive,implying it can use mechani-cal stresses to trigger certain physiological responses in the form of electric signals.Mechanotransduction l...Almost every life form,from the tiniest bacterium to humans,is mechanosensitive,implying it can use mechani-cal stresses to trigger certain physiological responses in the form of electric signals.Mechanotransduction largely relies on ion channels that respond to mechanical forces,such as the epithelial sodium channels/degenerins,tran-sient receptor potential channel,and the two-pore domain potassium channel.Piezo1 and Piezo2 proteins were discovered to be the biggest non-selective mechanosensitive cation channels in the cell membrane.A substantial amount of research has previously been published on the Piezo channel’s function in touch sensation,balance,and cardiovascular regression.However,the mechanistic perspective must be refined to fully understand the role of Piezo proteins in tissue engineering.This review centers on the latest insights into the structure of Piezo chan-nels,activation mechanisms,and its interactions with cytoskeletal components,by emphasizing the physiological activities of Piezo channels in different tissues.The study also places focus on the possibilities of targeting this cation channel family as a tissue regeneration aid.展开更多
Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodyn...Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia.However,mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood.In the present study,we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity.Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting(RA)mechanically-activated(MA)currents in rat dorsal root ganglion(DRG)neurons.We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension(SPMT)of these cells following vincristine treatment.Reducing SPMT of DRG neurons by cytochalasin D(CD),a disruptor of the actin filament,abolishes vincristine-induced potentiation of PIEZO2 MA currents,and suppresses vincristine-induced mechanical hypersensitivity in rats.Collectively,enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristineinduced mechanical allodynia and hyperalgesia in rats.Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.展开更多
文摘Almost every life form,from the tiniest bacterium to humans,is mechanosensitive,implying it can use mechani-cal stresses to trigger certain physiological responses in the form of electric signals.Mechanotransduction largely relies on ion channels that respond to mechanical forces,such as the epithelial sodium channels/degenerins,tran-sient receptor potential channel,and the two-pore domain potassium channel.Piezo1 and Piezo2 proteins were discovered to be the biggest non-selective mechanosensitive cation channels in the cell membrane.A substantial amount of research has previously been published on the Piezo channel’s function in touch sensation,balance,and cardiovascular regression.However,the mechanistic perspective must be refined to fully understand the role of Piezo proteins in tissue engineering.This review centers on the latest insights into the structure of Piezo chan-nels,activation mechanisms,and its interactions with cytoskeletal components,by emphasizing the physiological activities of Piezo channels in different tissues.The study also places focus on the possibilities of targeting this cation channel family as a tissue regeneration aid.
基金supported by NSFC grant 81571080(Zhanfeng Jia,China),81872848(Wei Zhang,China)the Central Government Guiding Local Funding Project for Scientific and Technological Development 206Z7703G(Zhanfeng Jia,China)+2 种基金Key Project and Cultivation Project of Precision Medicine Joint Fund of Natural Science Foundation of Hebei Province H2021206406(Zhanfeng Jia,China),H2022206211(Wei Zhang,China)and H2020206165(Zhanfeng Jia,China)Science and Technology Project of Hebei Education Department ZD2020107(Zhanfeng Jia,China)Science Fund for Creative Research Groups of Natural Science Foundation of Hebei Province H2020206474,China.
文摘Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia.However,mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood.In the present study,we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity.Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting(RA)mechanically-activated(MA)currents in rat dorsal root ganglion(DRG)neurons.We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension(SPMT)of these cells following vincristine treatment.Reducing SPMT of DRG neurons by cytochalasin D(CD),a disruptor of the actin filament,abolishes vincristine-induced potentiation of PIEZO2 MA currents,and suppresses vincristine-induced mechanical hypersensitivity in rats.Collectively,enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristineinduced mechanical allodynia and hyperalgesia in rats.Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.
