Perilipin 2 Protects against Lipotoxicity-Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype Changes.
Biomed Res Int
; 2022: 4581405, 2022.
Article
en En
| MEDLINE
| ID: mdl-35845956
ABSTRACT
Aims:
We explored whether and how perilipin 2 (Plin2) protected islets against lipotoxicity-induced islet dysfunction by regulating islet stellate cells (ISCs) activation.Methods:
Six-week-old male rats were given a high-fat diet or a control diet for 28 weeks. Glucose metabolic phenotypes were assessed using glucose/insulin tolerance tests, masson, and immunohistochemical staining. ISCs activation levels were assessed from rats and palmitic acid- (PA-) treated cultured ISCs by immunofluorescence, Oil red O staining, electron microscopy, quantitative PCR, and western blotting. Changes in ISCs phenotype of activation degree and its underlying mechanisms were assessed by target gene lentiviral infection, high-performance liquid chromatography (HPLC), and western blotting.Results:
Obese rats showed glucose intolerance, decreased endocrine hormone profiles, and elevated expression of α-smooth muscle actin (α-SMA), a polygonal appearance without cytoplasmic lipid droplets of ISCs in rats and isolated islets. PA-treated cultured ISCs exhibited faster proliferation and migration abilities with the induction of mRNA levels of lipid metabolism proteins, especially Plin2. The overexpression of Plin2 resulted in ISCs "re-quiescent" phenotypes associated with inhibition of the Smad3-TGF-ß signaling pathways.Conclusions:
Our observations suggest a protective role of Plin2 in weakening ISCs activation. It may serve as a novel therapeutic target for preventing islet fibrosis for T2DM.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Estrelladas Pancreáticas
/
Glucosa
Límite:
Animals
Idioma:
En
Revista:
Biomed Res Int
Año:
2022
Tipo del documento:
Article
País de afiliación:
China