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991.
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993.
Weijun Li Zhenhong Zhu Kai He Xiaoyu Ma Robert J. Pignolo Gary C. Sieck Jinghua Hu Haitao Wang 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(24)
Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models—Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)−/−, Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)−/−, and Pax7-Arl3−/−—by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3−/− mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3−/− and Pax7-Arl3−/− mice or primary isolated Myf5-Arl3−/− and Pax7-Ift88−/− myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway.Exercise is considered as the primary intervention to improve muscle strength and to counteract muscle atrophy. While physical exercise training is considered a suitable intervention to improve muscle strength and endurance in healthy individuals, some people are resistant to the beneficial effects of exercise (1–3). It has been debated whether exercise is beneficial or harmful for patients with myopathic disorders (4) and type 2 diabetes (5). This so-called “exercise resistance” is considered congenital, and one recently identified causative factor involved in exercise resistance is hepatokine selenoprotein P (2, 6).Primary cilia have a mechanosensory function in bone cells (7), renal cells (8), and airway smooth muscle cells exert a role in sensing oscillatory fluid flow and transducing extracellular mechano-chemical signals into intracellular biochemical responses (9). Intriguingly, low muscle tone is a clinical feature often present in congenital ciliopathies with unclear underlying mechanisms (10). Arf-like Protein 3 (ARL3) is a highly conserved ciliary protein across ciliated organisms. ARL3, a regulator of intraflagellar transport in primary cilia, has been reported involving with various ciliary signaling functions (11, 12) and maintaining cell division polarity (13). Arl3 mutations cause Joubert syndrome (14, 15). Arl3−/− knockout does not affect cilia structure but compromises ciliary function (16).Cells utilize primary cilia to convert environmental cues, mechanical or chemical, into various cellular signaling essential for development (17–21). During skeletal muscle development, Hedgehog (Hh) signaling helps to initiate the myogenic program (22). In myoblast cells, Fu et al. (23) showed that primary cilia are assembled during the initial stages of myogenic differentiation but disappear as cells progress through myogenesis. The ablation of primary cilia suppresses Hh signaling and myogenic differentiation while enhancing proliferation. However, there are still significant gaps in our understanding of how exercise and mechanical signals activate the Hh signaling pathway. In the present study, we hypothesize that primary cilia in satellite cells (SCs) transduce mechanical stimulation through activation of Hh signaling and promote muscle hypertrophy induced by exercise.Hypertrophy of skeletal muscle is a complex biological process that involves multiple cell types, including SCs, fibro-adipogenic precursors, endothelial cells, fibroblasts, pericytes, and immune cells. Removing cilia from fibro-adipogenic precursors can reduce intramuscular adipogenesis and increase myofibril size during muscle healing (24). SCs play an essential role in muscle hypertrophy and exercise adaptation (25, 26), especially in young mice (27). Mechanical signals can interrupt SC suppression in a skeletal muscle loss model induced by ovariectomy. Diminished SC number and elevated adipogenic gene expression in muscle caused by ovariectomy are averted by mechanical stimulation (28). Experiments in vitro indicate that mechanical stimulation enhances the fusion of SCs (29). SCs are a heterogeneous population of stem cells and committed progenitors (30). Paired box protein Pax-7 (Pax7) is a traditional marker of SCs and acts at different levels in a nonhierarchical regulatory network controlling SC-mediated muscle hypertrophy (31). A major target gene of Pax7 is Myogenic factor 5 (Myf5), and loss of Pax7 significantly decreases Myf5 expression in myoblasts (32). However, Myf5 is present in Pax3/Pax7 double mutants, indicating Myf5 activation occurs independently of Pax3/Pax7 (33). Furthermore, 10% of Pax7-expressing satellite cells have never expressed Myf5 (30). Parise et al. (34) observed an approximately sixfold increase in the number of Myf5-expressing cells by 48 h following exercise, which remained elevated until at least 96 h after exercise. We established three mouse models of Myf5-Arl3−/−, Pax7-Intraflagellar transport protein 88 homolog (Ift88−/−), and Pax7-Arl3−/− to investigate the SC during mechanical stimulation and exercise. In the present study, we provide exciting evidence that SC cilia act as the key mechanical sensor for exercise-induced hypertrophy. 相似文献
994.
目的 探讨儿童髓鞘少突胶质细胞糖蛋白(MOG)抗体相关炎性脱髓鞘疾病(IDD)患儿的临床表现、影像学特征、治疗方案及临床预后.方法 选择2014年6月1日至2020年9月30日,在中山大学孙逸仙纪念医院儿科确诊的7例MOG抗体相关IDD患儿为研究对象.其中,女性患儿为2例,男性为5例;平均年龄为8.3岁.回顾性分析该7... 相似文献
995.
目的:探讨老年性乳腺癌综合治疗的特殊性和重要性.方法:针对91例老年性乳腺癌患者选用不同的综合治疗手段.结果:有伴随疾病的老年患者选择缩小手术范围,以内分泌治疗为主的综合治疗措施,可收到较好的疗效.结论:老年性乳腺癌患者可依据患者个体化情况选择较为灵活的治疗手段. 相似文献
996.
目的评价4%氯硝柳胺乙醇胺盐粉剂在山丘地区杀灭钉螺效果。方法在石台县山丘地区选择沟渠和坡地等有代表性的有螺环境,分别采用4%氯硝柳胺乙醇胺盐粉剂喷粉(50g/m2)不清理环境施药和50%氯硝柳胺乙醇胺盐可湿性粉剂喷洒(2g/m2)法分别进行清理环境和不清理环境施药灭螺,于施药后3、7、15天观察钉螺死亡情况。结果在沟渠环境中,灭螺后3d、7d、15d,粉剂灭螺效果显著高于可湿性粉剂不清障喷洒灭螺效果(χ2=20.8362~77.8524,P<0.005),与可湿性粉剂清障喷洒灭螺效果无显著差异(χ2=0.1542~3.2426,P>0.05);在坡地环境中,灭螺后3d、7d、15d,粉剂灭螺效果均显著高于可湿性粉剂不清障喷洒和清障喷洒灭螺效果(χ2=60.3545~212.8355,P>0.005)。结论氯硝柳胺乙醇胺盐粉剂喷粉灭螺效果在不清障的情况下与可湿性粉剂喷洒灭螺效果相当,但在清障的情况下其效果显著高于可湿性粉剂喷洒灭螺,且适用于水源缺乏地区灭螺,因此具有显著的实际应用价值。 相似文献
997.
目的 比较分析原发性震颤(ET)合并帕金森病(PD)与ET、PD的震颤特征。方法 选取2019年1月—2021年1月郑州市某医院神经内科收治的100例住院患者为研究对象,根据患者疾病情况分为A组(ET合并PD,34例)、B组(ET,33例)、C组(PD,33例)。采用震颤评分量表(TRS)与肌电图仪收集患者静止、姿势与... 相似文献
998.
目的 比较Victoria blue法(A组)和Verhoeff法(B组)弹力纤维染色在染色过程、染色时间、染色效果方面对肺癌胸膜侵犯和结直肠癌浆膜或静脉侵犯判读的差异。方法 A组、B组均分别纳入肺癌怀疑胸膜侵犯标本50例和结直肠癌怀疑浆膜或静脉侵犯标本20例,进行弹力纤维染色。对比2组染色过程、染色时间、染色效果;根据染色稳定性、清晰度、对比度等综合评价胸膜侵犯和浆膜或静脉侵犯情况,并对染色质量及判读准确性进行评分。结果 A组比B组操作简单,染色质量稳定,肿瘤细胞与脏层胸膜、浆膜或静脉的关系显示更清晰。A组判读评分高于B组,差异有统计学意义(P<0.05)。结论 Victoria blue法染色有助于准确评估肺癌的胸膜侵犯和结直肠癌浆膜或静脉的侵犯,提高判读准确性。 相似文献
999.
雄性SD大鼠随机分为5组:25℃对照组,37℃每天2h共7天热适应组,42℃分别受热30min、60min,90min的3个热处理组。检测全血淋巴细胞转化率、α-醋酸萘酯酶活性、腹腔巨噬细胞活性和吞噬功能。结果显示:7天热适应组与受热30min组即明显降低,随受热时间延长(超过30min),巨噬细胞吞噬功能显著降低,不能形成吞噬峰。7天热适应组与受热30min组用PHA刺激全血淋巴细胞转化的刺激指数比对照组稍高,但差异不明显(P>0.05),而60min和90min受热却使该指数显著下降(P分别为0.0031和0.0063)。α-醋酸萘酯酶除热适应组降低外,其余各组无明显变化。结果提示,急性受热时机体免疫系统功能有受抑制倾向。 相似文献
1000.