title: Fibroin and sericin from Bombyx mori silk stimulate cell migration through upregulation and phosphorylation of c-Jun.
abstract: Wound healing is a biological process directed to the restoration of tissue that has suffered an injury. An important phase of wound healing is the generation of a basal epithelium able to wholly replace the epidermis of the wound. A broad range of products derived from fibroin and sericin from Bombyx mori silk are used to stimulate wound healing. However, so far the molecular mechanism underlying this phenomenon has not been elucidated. The aim of this work was to determine the molecular basis underlying wound healing properties of silk proteins using a cell model. For this purpose, we assayed fibroin and sericin in a wound healing scratch assay using MDA-MB-231 and Mv1Lu cells. Both proteins stimulated cell migration. Furthermore, treatment with sericin and fibroin involved key factors of the wound healing process such as upregulation of c-Jun and c-Jun protein phosphorylation. Moreover, fibroin and sericin stimulated the phosphorylation of ERK 1/2 and JNK 1/2 kinases. All these experiments were done in the presence of specific inhibitors for some of the cell signalling pathways referred above. The obtained results revealed that MEK, JNK and PI3K pathways are involved in fibroin and sericin stimulated cells migration. Inhibition of these three kinases prevented c-Jun upregulation and phosphorylation by fibroin or sericin. Fibroin and sericin were tested in the human keratinocyte cell line, HaCaT, with similar results. Altogether, our results showed that fibroin and sericin initiate cell migration by activating the MEK, JNK and PI3K signalling pathways ending in c-Jun activation.
authors.affiliation: Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario, La Alberca, Murcia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Martínez-Mora
authors.forename: Anna
authors.initials: A
authors.lastname: Mrowiec
authors.forename: Eva María
authors.initials: EM
authors.lastname: García-Vizcaíno
authors.forename: Antonia
authors.initials: A
authors.lastname: Alcaraz
authors.forename: José Luis
authors.initials: JL
authors.lastname: Cenis
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Nicolás
mesh_terms: D000818:Animals; D012831:Bombyx; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005349:Fibroins / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D047030:Sericins / Q000502:physiology*; D047011:Silk / Q000737:chemistry*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D047030:Sericins; D047011:Silk; D005349:Fibroins; D011494:Protein Kinases