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 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.
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Shinsuke
S
Matsuzaki
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan.
Toru
T
Hiratsuka
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan.
Manabu
M
Taniguchi
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Research & Development, Noevir Co., Ltd., Higashiomi, Shiga, Japan.
Kenta
K
Shingaki
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan.
Tateki
T
Kubo
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan.
Koichiro
K
Kiya
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan.
Toshihiro
T
Fujiwara
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan.
Shigeyuki
S
Kanazawa
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Ryutaro
R
Kanematsu
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan.
Tameyasu
T
Maeda
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Hironori
H
Takamura
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Kohe
K
Yamada
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Ko
K
Miyoshi
Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan.
Ko
K
Hosokawa
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Division of Molecular Brain Science, Research Institute of Traditional Oriental Medicine, Kinki University, Sayama, Osaka, Japan.
Masaya
M
Tohyama
Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Taiichi
T
Katayama
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts; D006025:Glycosaminoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D006025:Glycosaminoglycans; D016212:Transforming Growth Factor beta; D003094:Collagen