Merck

Physiological ER Stress Mediates the Differentiation of Fibroblasts.

PloS one (2015-05-01)
Shinsuke Matsuzaki, Toru Hiratsuka, Manabu Taniguchi, Kenta Shingaki, Tateki Kubo, Koichiro Kiya, Toshihiro Fujiwara, Shigeyuki Kanazawa, Ryutaro Kanematsu, Tameyasu Maeda, Hironori Takamura, Kohe Yamada, Ko Miyoshi, Ko Hosokawa, Masaya Tohyama, Taiichi Katayama
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Gastrin Releasing Peptide human, ≥97% (HPLC)
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose and sodium bicarbonate, without L-glutamine, sodium pyruvate, and phenol red, liquid, sterile-filtered, suitable for cell culture