Let-7b regulates alpaca hair growth by downregulating ectodysplasin A

Abstract

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.

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

“…Furthermore, HFD can accelerate both the anagen and telogen phases, shorten the hair growth cycle, and induce lipid droplet accumulation, ROS generation, and NF-κB signaling pathway activation in hair follicle stem cells (Morinaga et al, 2021). Liu et al (2018) revealed that EDA mRNA and protein expression was higher in ear skin than in back skin. Moreover, alpaca ear hair is thick and straight with a long growth cycle, but its back hair is long, curved, and has a short growth cycle (Liu et al, 2011); these differences in growth cycle duration between the alpaca ear and back hair may be related to differential EDA expression.…”

MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated ERK signaling in psoriasis

“…Recent study demonstrated that let-7b stimulates differentiation and prevents metaplasia by regulating HNF6 expression in pancreatic acinar cells [ 14 ]. It is also becoming increasingly recognized that let-7b plays an important role in hair growth [ 15 , 16 ], cutaneous wound healing [ 17 ] and skin disease [ 18 ]. Recently, it was found that let-7b inhibits keratinocyte migration through targeting IGF2BP2 [ 17 ].…”

The Roles of Non-coding RNA in the Development and Regeneration of Hair Follicles: Current Status and Further Perspectives

“…In an alpaca model, the expression level of the miRNA let-7b was shown to be negatively correlated with EDA expression levels in ear and back hair. Overexpression of let-7b causes reductions in EDA mRNA and protein levels, indicating that let-7b regulates HF development in alpaca cells by targeting the EDA gene, which is also associated with hypohidrotic ectodermal dysplasia ( Liu et al, 2018 ). Let-7b also modulates EDA expression by post-transcriptionally regulating TGF-β receptor I via a different mechanism ( Yan et al, 2016 ).…”