LncRNA H19 inhibited dermal papilla cell senescence process through miR-29a by targeting Wnt/β-catenin signaling pathway

Androgenetic alopecia is a common type of hair loss disease. As the most promising seeder for cell-based therapy, dermal papilla cells are prone to undergo premature senescence during passaging in vitro. Our previous studies revealed high expression of lncRNA H19 in early-passage dermal papilla cells and the maintenance of hair follicle-inducing ability upon prolonged culture. However, the exact mechanism of H19 regulating Wnt signaling pathway related to hair follicle regeneration has not been fully elucidated. Here, a cell senescence model was constructed by continuous cultivation in vitro to investigate the molecular mechanism of H19 in human dermal papilla cells. Animal hair follicle inductivity, cell proliferation and molecular experiments were performed to evaluate the cell inductivity, proliferation, senescence, expression of Wnt signaling key factors in early- and late-passage dermal papilla cells. Ectopic expression and silencing experiments were conducted to estimate effects of H19 on the proliferation and senescence of dermal papilla cells and the possible mechanism. Hair follicles from frontal baldness-prone and occipital non-balding areas of patients with androgenetic alopecia were exploited to detect the expression of H19 and relevant factors. Results showed late-passage DP8 cells exhibited lost hair follicle inductive properties, attenuated cell proliferation, elevated senescent marker and key Wnt factor levels, decreased inducing marker levels. Furthermore, overexpression of H19 inhibited senescence marker expression by binding to SAHH to upregulate miR-29, thus activating the Wnt signaling pathway to maintain inducing ability of DP cells. Knockdown of H19 showed opposite experimental results. Consistently, H19 together with miR-29a levels were lower and the expression levels of miR-29a target genes (DKK1, SFRP2) increased in the dermal papilla cells from frontal baldness-prone and occipital non-balding areas. Conclusively, our data provide a novel insight into the regulation and mechanism of H19 in inhibiting dermal papilla cell senescence, suggesting a potential therapy strategy for androgenetic alopecia.