Fibroblast growth factor homologous factor 1 stimulates Leydig cell regeneration from stem cells in male rats
Fibroblast growth factor homologous factor 1 stimulates Leydig cell regeneration from stem cells in male rats
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成纤维细胞生长因子同源因子 1 刺激雄性大鼠干细胞再生 Leydig 细胞
DOI：
10.1111/jcmm.14461
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发表时间：
2019-08-01
影响因子：
5.3
通讯作者：
Ge, Ren-Shan
中科院分区：
文献类型：
--
作者：
Mo, Jiaying;Chen, Xiuxiu;Ge, Ren-Shan
成纤维细胞生长因子同源因子1（FHF 1）是一种不与细胞表面成纤维细胞生长因子受体结合的细胞内蛋白。在这里，我们报告说，FHF 1是丰富的存在于Leydig细胞在其发展过程中上调。成年雄性Sprague道利大鼠腹腔注射75 mg/kg乙烷二甲烷磺酸盐（EDS），以消融Leydig细胞，启动其再生。然后，从EDS后第14天开始，大鼠每天接受睾丸内注射FHF 1（0、10和100 ng/睾丸），持续14天。FHF 1增加血清睾酮水平，但不影响促黄体生成素和促卵泡激素的水平。FHF 1增加了与HSD 11 B1（晚期Leydig细胞的生物标志物）染色的细胞数量，而不影响与CYP 11 A1（所有Leydig细胞的生物标志物）染色的细胞数量。FHF 1不影响Leydig细胞的PCNA标记指数。FHF 1可增加睾丸间质细胞Lhcgr、Scarb 1、星星、Cyp 11 a1、Hsd 3b 1、Cyp 17 a1、Hsd 17 b3、Insl 3、Nr 5a 1和Hsd 11 b1的mRNA及其蛋白水平。FHF 1增加前脂肪细胞生物标志物Dlk 1 mRNA水平，降低完全分化的脂肪细胞生物标志物（Fabp 4和Lpl）mRNA及其蛋白水平。总之，在EDS处理的睾丸中，FHF 1促进间质细胞从干细胞再生，同时抑制前脂肪细胞/干细胞分化为脂肪细胞。
Fibroblast growth factor homologous factor 1 (FHF1) is an intracellular protein that does not bind to cell surface fibroblast growth factor receptor. Here, we report that FHF1 is abundantly present in Leydig cells with up-regulation during its development. Adult male Sprague Dawley rats were intraperitoneally injected with 75 mg/kg ethane dimethane sulphonate (EDS) to ablate Leydig cells to initiate their regeneration. Then, rats daily received intratesticular injection of FHF1 (0, 10 and 100 ng/testis) from post-EDS day 14 for 14 days. FHF1 increased serum testosterone levels without affecting the levels of luteinizing hormone and follicle-stimulating hormone. FHF1 increased the cell number staining with HSD11B1, a biomarker for Leydig cells at the advanced stage, without affecting the cell number staining with CYP11A1, a biomarker for all Leydig cells. FHF1 did not affect PCNA-labelling index in Leydig cells. FHF1 increased Leydig cell mRNA (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Insl3, Nr5a1 and Hsd11b1) and their protein levels in vivo. FHF1 increased preadipocyte biomarker Dlk1 mRNA level and decreased fully differentiated adipocyte biomarker (Fabp4 and Lpl) mRNA and their protein levels. In conclusion, FHF1 promotes Leydig cell regeneration from stem cells while inhibiting the differentiation of preadipocyte/stem cells into adipocytes in EDS-treated testis.