The biomolecular basis of adipogenic differentiation of adipose-derived stem cells.

The biomolecular basis of adipogenic differentiation of adipose-derived stem cells.
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DOI:
10.3390/ijms15046517
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发表时间:
2014-04-16
影响因子:
5.6
通讯作者:
Orlandi A
Orlandi A
中科院分区:
生物学2区
文献类型:
--
作者:
Scioli MG;Bielli A;Gentile P;Mazzaglia D;Cervelli V;Orlandi A

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受体信号传导和下游调节介质在脂肪细胞稳态中的作用引起了相当大的关注,但关于脂肪源性干细胞(ASC)生物学的信息较少。最近的研究表明,调控ASC分化的途径涉及受体酪氨酸激酶(RTK)的活性,包括成纤维细胞生长因子、血管内皮生长因子、Erb B受体和下游调节的丝氨酸/苏氨酸蛋白激酶B(Akt)以及磷酸酶和张力蛋白同源物(PTEN)活性。RTK是细胞表面受体,代表细胞稳态的关键调节因子,但也在癌症进展中起关键作用。活化的RTK的许多代谢作用和其他后果是由Akt和细胞外信号调节蛋白激酶1(Erk-1)信号传导的调节介导的。Akt活性维持ASCs的存活和成脂分化,而Erk-1出现下调。FGFR-1、EGFR和ErbB 2的抑制降低了增殖,但只有FGFR-1抑制剂降低了Akt活性和脂肪形成。脂肪生成和新血管形成也是时间和空间上耦合的过程,并且RTK激活和下游靶点也参与ASC介导的血管生成。ASC的潜力和调节ASC生物学过程的特定分子途径的可能性,特别是与癌细胞共享的分子途径,为再生医学领域提供了新的令人兴奋的策略。
There is considerable attention regarding the role of receptor signaling and downstream-regulated mediators in the homeostasis of adipocytes, but less information is available concerning adipose-derived stem cell (ASC) biology. Recent studies revealed that the pathways regulating ASC differentiation involve the activity of receptor tyrosine kinases (RTKs), including fibroblast growth factor, vascular endothelial growth factor, ErbB receptors and the downstream-regulated serine/threonine protein kinase B (Akt) and phosphatase and tensin homolog (PTEN) activity. RTKs are cell surface receptors that represent key regulators of cellular homeostasis but also play a critical role in the progression of cancer. Many of the metabolic effects and other consequences of activated RTKs are mediated by the modulation of Akt and extracellular signal-regulated protein kinases 1 (Erk-1) signaling. Akt activity sustains survival and the adipogenic differentiation of ASCs, whereas Erk-1 appears downregulated. The inhibition of FGFR-1, EGFR and ErbB2 reduced proliferation, but only FGFR-1 inihibition reduced Akt activity and adipogenesis. Adipogenesis and neovascularization are also chronologically and spatially coupled processes and RTK activation and downstream targets are also involved in ASC-mediated angiogenesis. The potentiality of ASCs and the possibility to modulate specific molecular pathways underlying ASC biological processes and, in particular, those shared with cancer cells, offer new exciting strategies in the field of regenerative medicine.
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