研究者情報

コタケ　ヒトシ   KOTAKE HITOSHI   小竹　徹    所属   医学部医学科 腎臓・高血圧内科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Angiotensin II type 1a receptor deficiency alleviates muscle atrophy after denervation
掲載誌名	正式名：Scientific Reports 略　 称：Sci Rep.
掲載区分	国外
出版社名	Nature Publishing Group
巻・号・頁	13(1),519頁
著者・共著者	Takayama S, Inoue K, Ogura Y, Hoshino S, Sugaya T, Ohata K, Kotake H, Ichikawa D, Watanabe M, Kimura K, Shibagaki Y, Kamijo‑Ikemori A.
発行年月	2023/01
概要	The study aim was to determine if suppressed activation of angiotensin II type 1 receptor (AT1) prevents severe muscle atrophy after denervation. The sciatic nerves in right and left inferior limbs were cut in AT1a knockout homo (AT1a−/−) male mice and wild-type (AT1a+/+) male mice. Muscle weight and cross-sectional areas of type IIb muscle fibers in gastrocnemius muscle decreased at 7 and 21 days postdenervation in both AT1a−/− mice and AT1a+/+ mice, and the reduction was significantly attenuated in the denervated muscles of AT1a−/− mice compared to the AT1a+/+ mice. Gene expressions in the protein degradation system [two E3 ubiquitin ligases (muscle RING-finger protein-1 and Atrogin-1)] upregulated at 7 days postdenervation in all denervated mice were significantly lower in AT1a−/− mice than in AT1a+/+ mice. Activations of nuclear factor κB and Forkhead box subgroup O1, and protein expression of monocyte chemoattractant protein-1 were significantly suppressed in the AT1a−/− mice compared with those in the AT1a+/+ mice. In addition, suppressed apoptosis, lower infiltration of M1 macrophages, and higher infiltration of M2 macrophages were significantly observed at 21 days postdenervation in the AT1a−/− mice compared with those in the AT1a+/+ mice. In conclusion, the AT1 receptor deficiency retarded muscle atrophy after denervation.
DOI	10.1038/s41598-023-27737-7
PMID	36627369