Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
Università Vita-Salute San Raffaele, Milano, Italy.
Endocrine. 2018 Oct;62(1):129-135. doi: 10.1007/s12020-018-1606-4. Epub 2018 May 30.
Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. The peptides produced by the ghrelin gene, i.e., acylated ghrelin (AG), unacylated ghrelin (UnAG), and obestatin (Ob), affect skeletal muscle biology in several ways, not always with overlapping effects. In particular, UnAG and Ob promote SC self-renewal and myoblast differentiation, thus fostering muscle regeneration.
To delineate the endogenous contribution of preproghrelin in muscle regeneration, we evaluated the repair process in Ghrl mice upon CTX-induced injury.
Although muscles from Ghrl mice do not visibly differ from WT muscles in term of weight, structure, and SCs content, muscle regeneration after CTX-induced injury is impaired in Ghrl mice, indicating that ghrelin-derived peptides actively participate in muscle repair. Remarkably, the lack of ghrelin gene impacts SC self-renewal during regeneration.
Although we cannot discern the specific Ghrl-derived peptide responsible for such activities, these data indicate that Ghrl contributes to a proper muscle regeneration.
肌肉再生依赖于卫星细胞（SCs），这些静止的前体细胞在受伤或肌肉疾病等病理状态下会被激活、增殖和分化，以修复受损组织。SCs 的一部分会进行自我更新，从而维持 SC 池及其再生潜能。胃饥饿素基因产生的肽，即酰化胃饥饿素（AG）、非酰化胃饥饿素（UnAG）和肥胖抑制素（Ob），以多种方式影响骨骼肌生物学，其作用并不总是重叠。特别是，UnAG 和 Ob 促进 SC 自我更新和成肌细胞分化，从而促进肌肉再生。
为了描绘 preproghrelin 在内源性肌肉再生中的贡献，我们评估了 CTX 诱导损伤后 Ghrl 小鼠的修复过程。
尽管 Ghrl 小鼠的肌肉在重量、结构和 SCs 含量方面与 WT 肌肉没有明显差异，但 Ghrl 小鼠在 CTX 诱导损伤后的肌肉再生受损，表明胃饥饿素衍生肽积极参与肌肉修复。值得注意的是，缺乏胃饥饿素基因会影响再生过程中的 SC 自我更新。
尽管我们无法确定导致这种活性的特定 Ghrl 衍生肽，但这些数据表明 Ghrl 有助于适当的肌肉再生。
