Physiological ER Stress Mediates the Differentiation of Fibroblasts

Recently, accumulating reports have suggested the importance of endoplasmic reticulum (ER) stress signaling in the differentiation of several tissues and cells, including myoblasts and osteoblasts. Secretory cells are easily subjected to ER stress during maturation of their secreted proteins. Skin f...

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Published in:	PloS one Vol. 10; no. 4; p. e0123578
Main Authors:	Matsuzaki, Shinsuke, Hiratsuka, Toru, Taniguchi, Manabu, Shingaki, Kenta, Kubo, Tateki, Kiya, Koichiro, Fujiwara, Toshihiro, Kanazawa, Shigeyuki, Kanematsu, Ryutaro, Maeda, Tameyasu, Takamura, Hironori, Yamada, Kohe, Miyoshi, Ko, Hosokawa, Ko, Tohyama, Masaya, Katayama, Taiichi
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 30-04-2015 Public Library of Science (PLoS)
Subjects:	Actin Animals Apoptosis Atrophy Biocompatibility Biomedical materials Blotting, Western Bone morphogenetic proteins Brain research Cell Differentiation - physiology Cell Survival - physiology Child development Children & youth Collagen Collagen - metabolism Contraction Dermatology Differentiation Disease Endoplasmic reticulum Endoplasmic Reticulum Stress - genetics Endoplasmic Reticulum Stress - physiology Families & family life Fibroblasts Gels Glycosaminoglycans Glycosaminoglycans - metabolism Immunohistochemistry Kinases Matrix metalloproteinases Medicine Mice, Inbred C57BL Mucopolysaccharides Muscle contraction Muscle proteins Muscles Myoblasts Myofibroblasts - cytology Myofibroblasts - metabolism Neurosciences Osteoblastogenesis Osteoblasts Physiological aspects Physiology Plastic surgery Proteins Quarks R&D Research & development Science Shrinkage Signal transduction Signaling Skin Smooth muscle Stress Stress (Physiology) Stress response Tissue inhibitor of metalloproteinases Tissues Transcription factors Transforming Growth Factor beta - metabolism Transforming growth factors University graduates Wound care Wound healing Japan
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Summary:	Recently, accumulating reports have suggested the importance of endoplasmic reticulum (ER) stress signaling in the differentiation of several tissues and cells, including myoblasts and osteoblasts. Secretory cells are easily subjected to ER stress during maturation of their secreted proteins. Skin fibroblasts produce and release several proteins, such as collagens, matrix metalloproteinases (MMPs), the tissue inhibitors of metalloproteinases (TIMPs) and glycosaminoglycans (GAGs), and the production of these proteins is increased at wound sites. Differentiation of fibroblasts into myofibroblasts is one of the key factors for wound healing and that TGF-β can induce fibroblast differentiation into myofibroblasts, which express α-smooth muscle actin. Well-differentiated myofibroblasts show increased production of collagen and TGF-β, and bring about wound healing. In this study, we examined the effects of ER stress signaling on the differentiation of fibroblasts, which is required for wound healing, using constitutively ER stress-activated primary cultured fibroblasts. The cells expressed positive α-smooth muscle actin signals without TGF-β stimulation compared with control fibroblasts. Gel-contraction assays suggested that ER stress-treated primary fibroblasts caused stronger shrinkage of collagen gels than control cells. These results suggest that ER stress signaling could accelerate the differentiation of fibroblasts to myofibroblasts at injured sites. The present findings may provide important insights for developing therapies to improve wound healing.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: SK is an employee of Noevir Co., Ltd. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: SM TK M. Tohyama KH. Performed the experiments: TH SM M. Taniguchi KS RK. Analyzed the data: TH SM M. Taniguchi KS TK KK TF SK TM HT KY KM TK M. Tohyama. Contributed reagents/materials/analysis tools: TH SM M. Taniguchi KS TK KK TF SK HT KY. Wrote the paper: TH SM.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0123578