Hypohidrotic ectodermal dysplasia (HED), also known as anhidrotic ectodermal dysplasia, is characterized by the clinical manifestations of less sweat or no sweat, sparse or no hair, tooth agenesis and/or abnormal tooth morphology. The characteristics of alpaca ear hair differ from the back hair. The ectodysplasin A (EDA) signaling pathway has a regulatory effect on skin development and hair growth. The aim of the present study was to study the effects of EDA on alpaca hair growth by examining the mRNA and protein expression levels of EDA in alpaca ear and back skin by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Results indicated that EDA expression was higher in the ear skin compared with the back skin. The expression levels of let‑7b in the skin of healthy alpacas varies; the difference between let‑7b expression levels of the ear and back have been reported to be >2‑fold, suggesting a role for let‑7b in the development of adult alpaca skin and hair follicles. A dual‑luciferase reporter vector was constructed to verify the targeting relationship between microRNA let‑7b and EDA, and the results revealed that EDA was a target gene of let‑7b. Alpaca skin fibroblasts were transfected with a let‑7b eukaryotic expression vector to investigate the regulatory relationship between let‑7b and EDA. The expression of EDA was decreased in the transfected group; immunocytochemical results demonstrated that the EDA protein was abundantly expressed in the fibroblast cytoplasm. EDA protein expression was weaker in the transfected cells than in the untransfected cells. These results suggested that EDA may serve a role in alpaca hair growth and is probably a target gene of let‑7b; let‑7b downregulated EDA mRNA and protein expressions, which suggested that let‑7b may regulate alpaca hair growth. These conclusions suggested that let‑7b may be associated with HED.

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast‐derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12‐derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid‐promoting factor peroxisome proliferator‐activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen‐1 and α‐smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12‐derived exosomes to SCs. Application of C2C12‐derived exosomes to fibro‐adipogenic progenitors resulted in an increase in peroxisome proliferator‐activated receptor γ expression and adipogenesis capacity, whereas α‐smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12‐derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome‐mediated regulation of the proliferation of SCs, differentiation of fibro‐adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition.

Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue.