The Journal of clinical investigation · 2022
A Piezo1/KLF15/IL-6 axis mediates immobilization-induced muscle atrophy.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hirata Yu, Nomura Kazuhiro, Kato Daisuke, Tachibana Yoshihisa, Niikura Takahiro, Uchiyama Kana, Hosooka Tetsuya, Fukui Tomoaki, Oe Keisuke, Kuroda Ryosuke, Hara Yuji, Adachi Takahiro, Shibasaki Koji, Wake Hiroaki, Ogawa Wataru
Аннотация
Although immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that Krüppel-like factor 15 (KLF15) and IL-6 are upregulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca2+ bioimaging revealed that the cytosolic Ca2+ concentration ([Ca2+]i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the downregulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies against IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobility-induced muscle atrophy was validated in human samples. Our results thus uncover a paradigm for Ca2+ signaling in that a decrease in [Ca2+]i from the basal level triggers a defined biological event.