Open AccessIRF3 signaling pathway serves an important role in poly(I:C)-induced procollagen reduction in human skin fibroblasts
Author(s) -
Yong Cheng,
Sun-Hee Han,
ChiHyun Park,
Yeji Kim,
Dong Hoon Lee,
Jin Ho Chung
Publication year - 2017
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2017.8136
Subject(s) - irf3 , tlr3 , signal transduction , biology , microbiology and biotechnology , interferon regulatory factors , pattern recognition receptor , innate immune system , receptor , rna silencing , interferon , toll like receptor , biochemistry , rna , immunology , rna interference , gene
Pattern recognition receptors (PRRs) are part of the immune system. They can recognize pathogen‑associated molecular patterns (PAMPs). Toll‑like receptors (TLRs) and retinoic acid‑inducible gene 1 (RIG‑1)‑like receptors (RLRs) are 2 types of PRR in the innate immune system. Double‑stranded RNA (dsRNA) can exist as a PAMP, including dsRNA viruses. dsRNA is known as a ligand not only for TLR3 but also for RLRs, including melanoma differentiation‑associated gene 5 and RIG‑1. Collagen is the main structural protein in the extracellular space in the skin. Recently, it was reported that treatment of a synthetic dsRNA, poly(I:C), decreases procollagen expression in skin fibroblasts. However, signaling pathways involved in this process have not yet been fully elucidated. The present study further explored the underlying signaling pathways involved in the processes. It was demonstrated by western blotting that treatment of poly(I:C), but not another PAMP, Pam3CSK4, inhibited procollagen expression in cultured human skin fibroblasts. Treatment of poly(I:C)and Pam3CSK4 induced activation of the mitogen‑activated protein kinases and the nuclear factor‑κB pathways. However, only poly(I:C), but not Pam3CSK4, induced the activation of the interferon regulatory factor 3 (IRF3) pathway. By using specific inhibitors, it was demonstrated that inhibition of IRF3 pathway relieved poly(I:C)‑induced procollagen reduction. In conclusion, IRF3 signaling pathway serves an important role in poly(I:C)‑induced procollagen reduction in skin fibroblasts. This suggests that the IRF3 signaling pathway may be a key target for collagen regulation in the skin.