| Autor: |
Kanai, Mai, Ganbaatar, Byambasuren, Endo, Itsuro, Ohnishi, Yukiyo, Teramachi, Jumpei, Tenshin, Hirofumi, Higa, Yoshiki, Hiasa, Masahiro, Mitsui, Yukari, Hara, Tomoyo, Masuda, Shiho, Yamagami, Hiroki, Yamaguchi, Yuki, Aihara, Ken-ichi, Sebe, Mayu, Tsutsumi, Rie, Sakaue, Hiroshi, Matsumoto, Toshio, Abe, Masahiro |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences; Jun2024, Vol. 25 Issue 11, p5715, 15p |
| Abstrakt: |
Chronic inflammation causes muscle wasting. Because most inflammatory cytokine signals are mediated via TGF-β-activated kinase-1 (TAK1) activation, inflammatory cytokine-induced muscle wasting may be ameliorated by the inhibition of TAK1 activity. The present study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG/Jcl mice as an autoimmune arthritis animal model were treated with a small amount of mannan as an adjuvant to enhance the production of TNF-α and IL-1β. The increase in these inflammatory cytokines caused a reduction in muscle mass and strength along with an induction of arthritis in SKG/Jcl mice. Those changes in muscle fibers were mediated via the phosphorylation of TAK1, which activated the downstream signaling cascade via NF-κB, p38 MAPK, and ERK pathways, resulting in an increase in myostatin expression. Myostatin then reduced the expression of muscle proteins not only via a reduction in MyoD1 expression but also via an enhancement of Atrogin-1 and Murf1 expression. TAK1 inhibitor, LL-Z1640-2, prevented all the cytokine-induced changes in muscle wasting. Thus, TAK1 inhibition can be a new therapeutic target of not only joint destruction but also muscle wasting induced by inflammatory cytokines. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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