Oral Presentation Australasian Society for Dermatological Research Annual Scientific Meeting 2017

An endogenous tryptophan photo-product, FICZ, is potentially integrated in photo-aging by reducing TGF-β-induced collagen maintenance (#12)

Mika Murai 1 , Gaku Tsuji 1 , Chikage Mitoma 1 , Takeshi Nakahara 1 , Hiroshi Uchi 1 , Masutaka Furue 1
  1. kyushu university, Maidashi, Higashi-ku, FUKUOKA, Japan

Background: Ultraviolet ray (UV) from the sun light causes photo-aging of the skin by reducing the amounts of type I collagen (COL1A1). Meanwhile, transforming growth factor (TGF)-β, a potent profibrotic cytokine, transforms dermal fibroblasts into α-smooth muscle actin (α-SMA)-expressing myofibroblasts and upregulates the COL1A1 production. The UV-mediated inhibitory mechanisms on the synthesis of COL1A1 are not fully understood. 6-formylindolo [3,2-b] carbazole (FICZ) is an endogenous tryptophan photo-metabolite generated by UV irradiation. FICZ is well known as a high affinity ligand for aryl hydrocarbon receptor (AHR). The physiological role of FICZ on photo-aging has not been investigated.

Purpose: To evaluate the effects of FICZ on the TGF-β-mediated COL1A1 and α-SMA expression in human dermal fibroblasts.

Methods: Quantitative RT-PCR and Western blot analysis were performed for the detection of COL1A1 and α-SMA with or without FICZ and TGF-β in normal human dermal fibroblasts (NHDFs). Immunofluorescence analysis is used for visualization of actin polymerization in myofibroblasts and evaluate the expression of phospholyrated-Smad2/3 protein.

Results: FICZ significantly inhibited the TGF-β-induced upregulation of mRNA and protein levels of COL1A1 and α-SMA. FICZ also inhibited the TGF-β-mediated actin polymerization in myofibroblasts. FICZ did not inhibit the phosphorylation of Smad2/3, which is a key downstream molecule of TGF-β signaling. However, FICZ did inhibit the translocation of cytoplasmic phosphorylated-Smad2/3 into nucleus. Notably, the inhibitory actions of FICZ on the TGF-β-mediated COL1A1 and nuclear translocation of phosphorylated-Smad2/3 were not affected by selective AHR antagonist CH223191, indicating that FICZ downregulated the COL1A1 maintenance by TGF-β in an AHR-independent manner.

Conclusion: An endogenous photoproduct FICZ may be integrated in photo-aging by inhibiting the TGF-β-mediated COL1A1 production. Downregulation of FICZ is a potential strategy to protect from photo-aging.

  • Are you currently a student: Yes
  • Are you currently a student: Yes