Wang Zixian, Liu Jianmin, Huang Yongmei, Liu Qian, Chen Meng, Ji Chunyan, Feng Jia, Ma Yi
Department of Cellular Biology, Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.
Department of Cellular Biology, Institute of Biomedicine, Jinan University, 601 Huangpu Avenue West, 510632, Guangzhou, China.
Stem Cell Rev Rep. 2023 Feb;19(2):516-530. doi: 10.1007/s12015-022-10415-y. Epub 2022 Sep 16.
Regenerative medicine and tissue engineering have delivered new healing possibilities to the treatment of soft tissue defects, but the selection of seed cells is critical for treatment. Adipose-derived stem cells have perpetually been a preferred candidate for seed cells due to their wealthy sources, simple access, high plasticity, and powerful value-added capabilities. How to improve the efficiency of adipogenic differentiation is the key to the treatment. Pituitary adenylate cyclase-activating peptide, as a biologically active peptide secreted by the pituitary, is widely involved in regulating the body's sugar metabolism and lipid metabolism. However, the effects of MPAPO in ADSCs adipogenic differentiation remain unknown. Our results reveal that MPAPO treatment improves the adipogenic differentiation efficiency of ADSCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipocyte protein biomarkers PPARγ and C/EBPa. Additionally, the mechanism studies showed that the effective window of MPAPO-induced adipogenesis was the first 3 days during ADSCs differentiation. MPAPO selectively binds to the PAC1 receptor and promotes adipogenic differentiation of ADSCs by activating the ERK signaling pathway and elevating cell proliferation during postconfluent mitosis stage. Altogether, we demonstrate that MPAPO plays a crucial role in ADSCs adipogenesis, providing experimental basis and data for exploring therapeutic options in tissue defect repair.
再生医学和组织工程为软组织缺损的治疗带来了新的愈合可能性，但种子细胞的选择对治疗至关重要。脂肪来源干细胞因其来源丰富、获取简便、可塑性高以及强大的增值能力，一直是种子细胞的首选。如何提高成脂分化效率是治疗的关键。垂体腺苷酸环化酶激活肽作为垂体分泌的一种生物活性肽，广泛参与调节机体的糖代谢和脂代谢。然而，MPAPO对脂肪来源干细胞成脂分化的影响尚不清楚。我们的结果表明，MPAPO处理可提高脂肪来源干细胞的成脂分化效率，包括促进脂滴和甘油三酯的积累以及脂肪细胞蛋白生物标志物PPARγ和C/EBPa的表达。此外，机制研究表明，MPAPO诱导成脂的有效窗口是脂肪来源干细胞分化的前3天。MPAPO选择性地与PAC1受体结合，并通过激活ERK信号通路和在汇合后有丝分裂阶段提高细胞增殖来促进脂肪来源干细胞的成脂分化。总之，我们证明MPAPO在脂肪来源干细胞成脂过程中起关键作用，为探索组织缺损修复的治疗选择提供了实验依据和数据。
