Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells.
Biochem Biophys Res Commun
; 439(2): 258-63, 2013 Sep 20.
Article
em En
| MEDLINE
| ID: mdl-23973482
ABSTRACT
The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive ß-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2-5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-ß and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.
Palavras-chave
4',6'-diamidino-2-phenylindole; 5-bromo-2-deoxyuridine; BrdU; CTGF; DAPI; DCF; DMEM; Diabetes mellitus; Dulbecco's Modified Eagle's Medium; ERK; FCS; GBSS; Gey's balanced salt solution; IL; Islet fibrosis; MAPK; OLETF; Otsuka Long-Evans Tokushima Fatty; Oxidative stress; PDGF; PKC; PSC; Pancreatic stellate cell; Pancreatic ß-cell; RAS; ROS; TGF-ß; TNF-α; connective tissue growth factor; dichloro-dihydrofluorescein diacetate; extracellular signal-regulated kinase; fetal calf serum; interleukin; mitogen-activated protein kinase; pancreatic stellate cell; platelet-derived growth factor; protein kinase C; reactive oxygen species; renin-angiotensin system; transforming growth factor-ß; tumor necrosis factor-α; α-SMA; α-smooth muscle actin
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Oxidativo
/
Células Estreladas do Pâncreas
/
Glucose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2013
Tipo de documento:
Article