关键词: Fhl1(Four and a half LIM domains protein 1)基因, 自噬, 肌纤维分化

Abstract: Objective To explore the effects of Fhl1 knockout (Fhl1-ko) on the differentiation and autophagy in gastrocnemius muscle in mice of different ages. Methods Wild-type (wt) and Fhl1-ko type male mice at 2.5-month-old and 8-month-old were studied and protein expressions of autophagy (Beclin-1), autophagic flux (increased LC3B-II/LC3B-I ratios and a lack of p62 accumulation) in gastrocnemius muscle were investigated by Western blotting. Transitions in myofiber phenotype in gastrocnemius muscle of Fhl1-ko mice at different ages were examined by real-time quantitative RT-PCR. Result Compared with wt mice, protein expression data showed that Beclin-1, LC3B-II/LC3B-I ratios were all increased in gastrocnemius muscle in Fhl1-ko mice at 2.5-month age. At the same time, p62 accumulation was not evident. LC3B-II/LC3B-I ratios were increased in gastrocnemius muscles in Fhl1-ko mice at 8-month age, but Beclin-1 was not clearly increase. Furthermore p62 accumulation was clearly evident. Transitions in the myofiber phenotype in the gastrocnemius muscle indicated MYH IIA and MYH IIX expression were decreased and MYH IIB increased in 2.5-month Fhl1-ko mice, compared with wt mice. However, MYH I and MYH IIA were both increased in 8-month Fhl1-ko mice compared with 8-month wt mice. Conclusion Effects of Fhl1-ko on the differentiation and autophagy in 2.5-month and 8-month gastrocnemius muscle were different which indicated regulation of autophagy might be a promising therapeutic target for hereditary myopathies induced by FHL1 and precise treatment should be used for patients of different ages.

Key words: Fhl1 (Four and a half LIM domains protein 1) gene, Autophagy