A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway.

Biochemical and biophysical research communications

PubMedID: 24928394

Wang J, Zhou J, Zhang N, Zhang X, Li Q. A heterocyclic molecule kartogenin induces collagen synthesis of human dermal fibroblasts by activating the smad4/smad5 pathway. Biochem Biophys Res Commun. 2014;.
BACKGROUND
Declined production of collagen by fibroblast is one of the major causes of aging appearance. However, only few of compounds found in cosmetic products were able to directly increase collagen synthesis. A novel small heterocyclic compound called kartogenin (KGN) is found to stimulate collagen synthesis of mesenchymal stem cells (MSCs). So, we hypothesized and tested that if KGN could be applied to stimulate the collagen synthesis of fibroblasts.

METHODS
Human dermal fibroblasts in vitro were treated with various concentrations of KGN, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to examine the expression of collagen and transforming growth factor beta (TGF-ß) signaling pathway. The production of collagen was also tested in vivo by Masson's trichrome stain and immunohistochemistry in the dermis of mice administrated with KGN.

RESULTS
Results showed that without obvious influence on fibroblasts' apoptosis and viability, KGN stimulated type-I collagen synthesis of fibroblasts at the mRNA and protein levels in a time-dependent manner, but KGN did not induce expression of a-skeletal muscle actin (a-sma) or matrix metallopeptidase 1 (MMP1), MMP9 in vitro. Smad4/smad5 of the TGF-ß signaling pathway was activated by KGN while MAPK signaling pathway remained unchanged. KGN also increased type-I collagen synthesis in the dermis of BALB/C mice.

CONCLUSION
Our results indicated that KGN promoted the type-I collagen synthesis of dermal fibroblasts in vitro and in the dermis of mice through activation of the smad4/smad5 pathway. This molecule could be used in wound healing, tissue engineering of fibroblasts, or aesthetic and reconstructive procedures.