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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01275

Leptin-induced angiogenesis of EA.hy926 endothelial cells via the Akt and Wnt signaling pathways in vitro and in vivo

 Fei Yu1, Runqing Fu2, Lu Liu2, Xiaoting Wang2, Tingting Wu2, Wei Shen3, Zhipeng Gui2, Xiumei Mo3, Bing Fang2 and Lunguo Xia2*
  • 1Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
  • 2Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, China
  • 3Donghua University, China

Angiogenesis involves the activation of endothelial cells followed by capillary formation. Leptin, the protein product of the ob gene, can induce the angiogenic potential of endothelial cells. However, the underlying cellular mechanism still remains to be elicited. We firstly evaluated the in vitro effects of leptin on proliferation and angiogenic differentiation of endothelial cell line EA.hy926. Leptin was found to potently induced cell proliferation, expression of angiogenic gene, migration and tube formation. Then we investigated the roles of the Akt and Wnt signaling pathways in the aforementioned processes. It showed that Akt and Wnt signaling pathways could be activated by leptin, while inhibition of the Akt and Wnt signaling pathways by siRNAs effectively blocked the leptin-induced angiogenesis. Finally, we used electrospinning to fabricated leptin-immobilized linear poly(L-lactide-co-caprolactone) (PLCL-leptin). The in vivo vessel formation of PLCL-leptin was evaluated using subcutaneous implants in Sprague-Dawley rats. The histological and immunofluorescence revealed that cell infiltration with PLCL-leptin was much more significant than that with the control PLCL group. More importantly, the number of laminin+ vessels and CD31+ cells in PLCL-leptin grafts was significantly higher than in control grafts. The study demonstrated that it is via Akt and Wnt signaling pathways that leptin promotes the proliferation and angiogenic differentiation of endothelial cells and the capacity of endogenous tissue regeneration makes the novel leptin-conjugated PLCL promising materials for grafts.

Keywords: Angiogenesis, Leptin, PLCL, Electrospinning, Tissue Engineering

Received: 07 Jul 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Yu, Fu, Liu, Wang, Wu, Shen, Gui, Mo, Fang and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Lunguo Xia, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, xialunguo@hotmail.com