title: BBF2H7-mediated Sec23A pathway is required for endoplasmic reticulum-to-Golgi trafficking in dermal fibroblasts to promote collagen synthesis.
abstract: Collagen fibers, structural elements responsible for mechanical strength in skin, are synthesized constitutively in response to cytokines such as IGF-I. However, little is known about their intracellular trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus during synthesis. We demonstrate herein that the BBF2 human homolog on chromosome 7 (BBF2H7)-mediated Sec23A pathway is involved in regulation of intracellular procollagen trafficking. The mRNA and protein expression of BBF2H7, Sec23A, and type I and III collagen (COL1 and COL3) was induced by IGF-I stimulation. In addition, the cleaved form of BBF2H7 was detected in IGF-I-treated cultures, indicating that activation occurs concurrently with its expression. Knockdown with small interfering RNAs targeting BBF2H7 caused a significant reduction in the expression of COL1 and COL3, regardless of IGF-I treatment. Both mitogen-activated protein kinase and phosphatidylinositol-3 kinase pathways via IGF-I receptor activation were required for BBF2H7 induction. Using immunofluorescence microscopy, we showed that Golgi apparatus dysmorphology is due to coat protein complex II vehicle hypoplasia caused by the absence of BBF2H7 and Sec23A. The BBF2H7-mediated Sec23A pathway was required for ER-to-Golgi procollagen trafficking to promote collagen synthesis. This role of growth factors such as IGF-I, which to our knowledge is previously unreported, suggests antiaging strategies.
authors.affiliation: DHC Corporation Laboratories, Division 2, Chiba, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ishikura-Kinoshita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tsuji-Naito
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D056811:Unfolded Protein Response; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C518609:CREB3L2 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; D034741:RNA, Small Interfering; C512739:SEC23A protein, human; D033921:Vesicular Transport Proteins; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases