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Perilipin 2 Protects against Lipotoxicity-Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype Changes.
Zhou, Yunting; Wang, Yuming; Ni, Chengming; Wang, Huiying; Zhou, Junming; Wan, Bingying; Li, Huiqin; Li, Fengfei; Huang, Rong; Xu, Wei; Shan, Ting; Cai, Tingting; Kong, Xiaoceng; Liu, Bingli; Liu, Xiaomei; Sun, Zilin; Ma, Jianhua.
Afiliación
  • Zhou Y; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Wang Y; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Ni C; Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
  • Wang H; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Zhou J; Department of Cadre Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
  • Wan B; Department of Nephrology, Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Changzhou, China.
  • Li H; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Li F; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Huang R; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Xu W; Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Xuzhou, China.
  • Shan T; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Cai T; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Kong X; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Liu B; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Liu X; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • Sun Z; Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
  • Ma J; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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.
Asunto(s)

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

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
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