Abstract
Wound healing is a dynamic and complex process. The proliferation and migration of dermal fibroblasts are crucial for wound healing. Recent studies have indicated that the extracts from Spirulina platensis have a positive potential for wound healing. However, its underlying mechanism is not fully understood. Our previous study showed that spirulina crude protein (SPCP) promoted the viability of human dermal fibroblast cell line (CCD-986sk cells). In this study, we further investigated the wound healing effect and corresponding mechanisms of SPCP on CCD-986sk cells. Bromodeoxyuridine (BrdU) assay showed that SPCP promoted the proliferation of CCD-986sk cells. The wound healing assay showed that SPCP promoted the migration of CCD-986sk cells. Furthermore, cell cycle analysis demonstrated that SPCP promoted CCD-986sk cells to enter S and G2/M phases from G0/G1 phase. Western blot results showed that SPCP significantly upregulated the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), and cyclin-dependent kinase 6 (Cdk6), as well as inhibited the expression of CDK inhibitors p21 and p27 in CCD-986sk cells. In the meanwhile, SPCP promoted the phosphorylation and activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt). However, the phosphorylation of Akt was significantly blocked by PI3K inhibitor (LY294002), which in turn reduced the SPCP-induced proliferation and migration of CCD-986sk cells. Therefore, the results presenting in this study suggested that SPCP can promote the proliferation and migration of CCD-986sk cells; the PI3K/Akt signaling pathway play a positive and important role in these processes.
Highlights
Skin mainly consists of epidermis and dermis, which acts as the largest organ of the human body against the outside environment [1]
The results showed that spirulina crude protein (SPCP) upregulated the expression of cyclin-dependent kinase 2 (Cdk2), cyclin-dependent kinase 4 (Cdk4), cyclin-dependent kinase 6 (Cdk6), cyclin D1, cyclin E, and pRb (Figure 3B,C, p < 0.05, p < 0.01, and p < 0.001), which are necessary for cell cycle
This result indicated that the cell migration induced by SPCP was blocked by LY294002
Summary
Skin mainly consists of epidermis and dermis, which acts as the largest organ of the human body against the outside environment [1]. Skin wounds disrupt the barrier between the inner body and outer surroundings, and lead to severe physical burdens upon human society [2]. Previous studies proved that wound healing is a dynamic and complex process, which requires an interaction between cell migration and cell proliferation relating to the regeneration and replacement of injured tissues [3,4]. The mechanical support and physical characteristics of the skin are dependent on the dermis [5]. It is necessary to develop an effective way for promoting the migration and proliferation of dermal fibroblasts. Mar. Drugs 2019, 17, 130; doi:10.3390/md17020130 www.mdpi.com/journal/marinedrugs
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