The transcriptional role of BBF2H7, ER stress transducer, during collagen biosynthesis in dermal fibroblasts

Abstract

BBF2 human homolog on chromosome 7 (BBF2H7), a member of the CREB/ATF family, is an endoplasmic reticulum (ER) stress transducer. BBF2H7 functions as a transcription factor to regulate expression of Sec23A, which encodes a coat protein complex II component responsible for protein transport from the ER to the Golgi. We have previously shown that BBF2H7 in normal human dermal fibroblasts (NHDFs) is involved in collagen synthesis in response to insulin growth factor-I (IGF-I), and that the BBF2H7-Sec23A pathway is required for ER-to-Golgi collagen trafficking. However, it is uncertain whether this pathway is also engaged in other cytokine stimulus-responsive collagen synthesis in dermal fibroblasts. Herein, we demonstrate a new pathway activating BBF2H7 in response to transforming growth factor-beta (TGF-β), which maintains dermal collagen homeostasis as well as IGF-I. TGF-β increased the expression levels of mRNA and protein of type I collagen (COL1) in NHDFs. The expression of BBF2H7 markedly elevated at earlier time points, whereas that of Sec23A was very similar to that of COL1. Furthermore, BBF2H7 knockdown caused a significant reduction in the expression of COL1 and Sec23A induced by TGF-β stimulation. These results suggest that BBF2H7 in NHDFs regulates the expression of COL1 and Sec23A in response to TGF-β. Pretreatment of SB431542, a specific TGF-β receptor type I kinase inhibitor, completely suppressed the expression of BBF2H7 and Sec23A induced by TGF-β stimulation, indicating that TGF-β-inducible activation of BBF2H7-Sec23A pathway is triggered by a ligand binding event. Our results raise the possibility that BBF2H7 plays a key role in dermal collagen synthesis constitutively regulated via several routes, contributing to provide novel anti-ageing strategies. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF