Nε-(carboxymethyl) lysine (CML), an advanced glycation end product (AGE), is an aging factor produced by glycation of protein. Higher levels of AGE in skin tissue are related to skin elasticity, but how CML that has accumulated in the skin affects hair follicle formation is unclear. This study constructed a simple model that mimics accumulated glycation from feeding by intradermally injecting Nε-(carboxymethyl) lysine (CML), and examined the effects on the morphogenesis of hair follicles (HF). The results showed weakening of the hair shaft and HF formation by CML. The in vitro inhibitory effect of CML on wound healing of dermal papilla cells (DPC) suggested that the mechanism influences the proliferation and migration of DPC, which are essential for HF morphogenesis. In addition, CML in DPC inhibited the expression of sonic hedgehog (Shh), a factor of tissue morphogenesis, in a NF-kBindependent manner. The findings suggest that the delay in HF formation was due to CML inhibiting proliferation and migration in DPC by inhibiting Shh expression.

It is generally accepted that Propionibacterium acnes (P. Acne) is involved in the development of acne, while the mechanisms of sebaceous lipogenesis and its control is unclear. Enterococcus faecalis FK-23 had shown to promote an anti-inflammatory action in several animal models. In the current study, we examined whether FK-23 modulate lipogenesis in sebocytes. FK-23 stimulated lipogenesis, while inhibited them in the presence of P. Acne. FK-23 acutely inhibited acetyl-CoA carboxylase (ACC) phosphorylation levels, while stimulated them with P. Acne. FK-23 stimulated PPARγ expression and activity, while inhibited them with P. Acne as pioglitazone did. These combined evidences demonstrated that the dual action by FK-23 on lipogenesis should reflect differentiation machinery prior to PPARγ, leading to producing adequate levels of sebum.