STAT3 operates as a novel transcription factor that regulates NEDD4 in Keloid

Abstract

Keloid, marked by excessive deposition of extracellular matrix components, usually occurs after cutaneous trauma. The molecular mechanism involved in the etiology of keloid remains largely unknown in spite of extensive studies presented on the mechanism of Keloid. NEDD4 has come to be recognized as a potential mediator implicated in inflammation and keloid that could chronically develop. Despite this, the working mechanism of NEDD4 involved in keloid remains unclear. In our present report, STAT3 was identified as a novel transcriptional factor that can diametrically regulate the transcription of NEDD4 and the translation that ensues. The regulation by STAT3 over NEDD4 can be abolished as long as the p-STAT3 was inactivated in the presence of Niclosamide, a kind of inhibitors that work specifically on STAT3 signaling pathway. In turn, silencing of NEDD4 was also shown to be able to down-regulate the expression of p-STAT3. No direct protein-protein interactions between STAT3 and NEDD4 can be identified in our setting. The data we provided herein enrich the knowledge regarding the molecular mechanism of NEDD4 involved in the pathogenesis of keloid, defining a new regulatory role for STAT3 in keloid.