Peptidyl-prolyl cis-trans isomerase FKBP10
endoplasmic reticulum
Inhibition of FKBP10 Attenuates Hypertrophic Scarring through Suppressing Fibroblast Activity and Extracellular Matrix Deposition.
Hypertrophic scar is a pathogenic form of scar formation with no recognized treatment to date. Its molecular mechanism is related to the abnormal proliferation and transition of fibroblasts and overproduction of extracellular matrix. FKBP10 is a molecular chaperone able to regulate α-smooth muscle actin expression and pro-collagen maturation in fibroblasts. However, to our knowledge, no research has investigated the biological function of FKBP10 in scar formation to date. In this study, we aim to assess the expression and function of FKBP10 in hypertrophic scarring. Through microarray analysis, real-time reverse transcriptase-PCR and immunohistochemistry, we discovered that FKBP10 is up-regulated in human and mouse hypertrophic scars. Then we evaluated hypertrophic scar formation in mouse models treated with FKBP10 small interfering RNA and found that knockdown of FKBP10 could attenuate hypertrophic scar formation in vivo. To further explore the underlying mechanism, FKBP10 was knocked down in human hypertrophic scar fibroblasts. The in vitro results showed that FKBP10 siRNA could inhibit fibroblast activity, reduce the expression of α-smooth muscle actin and extracellular matrix components, and attenuate transforming growth factor-β1 expression and the activation of the Smad signaling pathway. In conclusion, FKBP10 plays a crucial role in hypertrophic scar formation and might be a therapeutic target for hypertrophic scars.