@misc{10481/108919,
year = {2025},
month = {11},
url = {https://hdl.handle.net/10481/108919},
abstract = {PIEZO channels are mechanical force sensors involved in various biological processes, including somatosensation. To date, only a few PIEZO-binding partners have been identified, including MyoD-family inhibitor proteins (MDFI and MDFIC). Here, we show that MDFIC2, a third member of the MDFI protein family with an as-yet-unknown function, is expressed in a subset of nociceptive sensory neurons. MDFIC2 modulates both PIEZO1 and PIEZO2 gating properties by slowing their kinetics and shifting mechanical sensitivity to higher forces. Interestingly, Mdfic2 is downregulated in mouse neuropathic pain models in which mechanical allodynia is a hallmark symptom. We found that intrathecal administration of adeno-associated virus vector encoding MDFIC2 cDNA reduces mechanical sensitivity and attenuates mechanical allodynia in the spared nerve injury neuropathic pain model. These findings demonstrate a mechanism for regulating mechanosensation and highlight a potential therapeutic route for treating mechanical allodynia.},
organization = {Medical Research Council},
organization = {Qatar National Research Fund NPRP13S-0209-200315},
organization = {Wellcome Grant 200183/ Z/15/Z},
organization = {General Program of the National Natural Science Foundation of China (Grant No. 82471279)},
organization = {Zhejiang Provincial Natural Science Foundation of China under Grants Nos. MS25H090058 and LZ24H030003},
organization = {European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 678610)},
organization = {NIHR Great Ormond Street Hospital Biomedical Research Centre (562868)},
organization = {UK Medical Research Council grants MR/R025134/1, MR/R015325/1, MR/S009434/1, MR/N026101/1, and MR/T044853/1)},
organization = {Institutional Strategic Support Fund/UCL Therapeutic Acceleration Support (204841/Z/16/Z)},
publisher = {PNAS},
keywords = {Piezo channel},
keywords = {Mechanical allodynia},
keywords = {Neuropathic pain},
title = {MDFIC2 is a PIEZO channel modulator that can alleviate mechanical allodynia associated with neuropathic pain},
doi = {10.1073/pnas.2512426122},
author = {Torres De Pinedo, Jesús Manuel and Habib, Abdella M and Shengman, Li and Zhan, Chenjing and Meijun, Ji and Osorio, Nancy and Penalba, Virginie and Gossage, Samuel J and Rezai, Mehdi A and Geard, Amy F and Rahim, Ahad A and Mahmoud, Ahmed MM and Santana-Varela, Sonia and Zhou, Jun and Zhao, Jing and Wood, John N. and Okorokov, Andrei L and Zhou, Xuelong and Cox, James J and Coste, Bertrand},
}