Lucilia Sricata

Mol Biol Rep DOI 10.1007/s11033-009-9806-x

Maggot excretions/secretions induces human microvascular endothelial cell migration through AKT1
Shou-yu Wang Æ Kai Wang Æ Yi Xin Æ De-cheng Lv

Received: 12 April 2009 / Accepted: 2 September 2009 Ó Springer Science+Business Media B.V. 2009

Abstract Maggot therapy is a simple and highly successful method for healing of infected and necroticwounds. The increasing evidences indicate that Maggot excretions/secretions (ES) plays important roles in the wounds healing process. But the precise molecular mechanisms remain undefined. Herein, we investigated if ES induced cell migration during wound healing process using microvascular endothelial cells (HMEC-1) as model, and this effect was associated with the activation of AKT1 and ERK1/2. Woundhealing and transwell migration assays were performed to study the effects of ES on HMEC-1 cell migration. Our data showed that ES significantly induced HMEC-1 cell migration in both wound healing and transwell assays, and time-dependently (P \ 0.05) activated AKT1, but not ERK1/2. Moreover LY294002 (a PI3K inhibitor) partially attenuated (P \ 0.05) ES-induced cell migration in wound healing assaywhile completely inhibited (P \ 0.05) ES-induced AKT1 activation. These findings demonstrate that ES directly induces HMEC-1 cell migration and this event is partially mediated by the activation of AKT1.

Keywords HMEC-1

ES Á Wound healing Á Migration Á AKT1 Á

Introduction Maggot therapy, also known as biosurgery, is a simple and highly successful method for healing of infected andnecrotic wounds. Use of maggots for wound debridement has a long history. Many cases on the use of maggots in the treatment of diabetic foot ulcers, chronic venous leg ulcers, surgical wounds, burns and osteomyelitis have been reported in the last decade [1–4]. Our group also performed a successful debridement of an infected wound after forearm replantation using maggot therapy [5]. The increasingevidence indicates that maggot excretions/secretions (ES) plays important roles in wounds healing process, including disinfection of the wound by antibacterial materials, promotion of tissue granulation and improvement of wound reparation [6, 7]. Currently, the antibacterial properties of the ES have been studied most extensively, and a hydrophilic substance with low molecular weight has been isolatedas the major antibacterial component [8, 9]. However, little is known about the effect of ES on the wound reparation. During wound reparation progress, a critical step is the migration of the resident epidermal keratinocytes and dermal cells from the wound edge and surrounding epidermis to the wound bed [10]. The dermal cells, including dermal fibroblasts and human dermal microvascular endothelialcells, perform important function in this reparation process. Recently, Smith AG and his colleagues found that Maggot ES markedly accelerated the migration of fibroblasts and epidermal keratinocytes during wound

Shou-yu Wang and Kai Wang contributed equally to this work. S. Wang Á D. Lv (&) Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Road,116011 Dalian, Liaoning, People’s Republic of China e-mail: kwasyw@yahoo.com K. Wang Department of Biochemistry, Dalian Medical University, 116044 Dalian, Liaoning, People’s Republic of China Y. Xin Department of Biotechnology, Dalian Medical University, 116044 Dalian, Liaoning, People’s Republic of China

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closure [11]. And they also implied that ES promoted human dermalneonatal fibroblast (HDNF) cell migration across a fibronectin-coated surface, which was contributed to the serine proteinase activities of ES [12]. But the signaling network mediating ES-regulated cell migration is poorly defined. It is well demonstrated that many cellular, extracellular, vascular and cytokine-related components trigger multiple downstream protein kinase pathways, thereby...