Effects of Adra2α expression of adipose stem cells on the treatment of type 2 diabetic mice.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-02-14 DOI:10.1186/s13287-025-04192-x

Xinzhen Zuo, Gaofan Meng, Lili Song, Xiao Dong

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Abstract

Background: Adipose stem cell (ASC) therapy has been tested as a new option for the treatment of type 2 diabetes (T2D). Our previous transcriptome sequencing analysis showed that the adrenergic α2 receptor (Adra2α) was highly expressed in ASCs from T2D mice compared to healthy controls. This study aims to explore the role of Adra2α on the characterization and therapeutic function of ASCs.

Methods: Clonidine (an Adra2α agonist) or si-RNA was used to observe Adra2α on ASCs proliferation, migration, growth factors (HGF, TGF-β1 and VEGF) expression and secretion. T2D mice were treated with non-treated control or Adra2α knockdown T2D ASCs (namely NC ASCs or KD ASCs). Mice glucose levels, insulin sensitivity and other metabolic indicators were measured and compared.

Results: Treatment of ASCs with Clonidine reduced the proliferation, migration, and growth factors expression and secretion of ASCs, while Adra2α knocking down ASCs showed opposite effects. This translated in vivo when T2D + KD ASCs could improve hyperglycemia and insulin resistance, reduce fat content in adipose tissues and livers, suppress body inflammation, and increase pancreatic β cell mass in T2D mice compared to NC ASCs.

Conclusions: Adra2α plays a critical role in regulating the proliferation, migration, and expression of growth factors of ASCs. Suppression of Adra2α expression in T2D ASCs restored/improved their therapeutic effects.

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脂肪干细胞Adra2α表达对2型糖尿病小鼠治疗的影响。

背景：脂肪干细胞（ASC）疗法已被证明是治疗2型糖尿病（T2D）的一种新选择。我们之前的转录组测序分析显示，与健康对照组相比，肾上腺素能α2受体（Adra2α）在T2D小鼠的ASCs中高表达。本研究旨在探讨Adra2α在ASCs的表征和治疗功能中的作用。方法：用可乐定（Adra2α激动剂）或si-RNA观察Adra2α对ASCs增殖、迁移、生长因子（HGF、TGF-β1、VEGF）表达和分泌的影响。用未处理的对照组或Adra2α敲低的T2D ASCs（即NC ASCs或KD ASCs）治疗T2D小鼠。测量和比较小鼠的葡萄糖水平、胰岛素敏感性和其他代谢指标。结果：可乐定治疗ASCs可降低ASCs的增殖、迁移、生长因子的表达和分泌，而Adra2α抑制ASCs则相反。在体内，与NC ASCs相比，T2D + KD ASCs可以改善T2D小鼠的高血糖和胰岛素抵抗，降低脂肪组织和肝脏中的脂肪含量，抑制机体炎症，增加胰腺β细胞质量。结论：Adra2α在ASCs的增殖、迁移和生长因子表达调控中起关键作用。抑制Adra2α在T2D ASCs中的表达可恢复/提高其治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.