Laminin 332 deposition is diminished in irradiated skin in an animal model of combined radiation and wound skin injury. Radiat Res 2011 Nov;176(5):636-48
Date
08/23/2011Pubmed ID
21854211Pubmed Central ID
PMC3227557DOI
10.1667/rr2422.1Scopus ID
2-s2.0-80155161949 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Skin exposure to ionizing radiation affects the normal wound healing process and greatly impacts the prognosis of affected individuals. We investigated the effect of ionizing radiation on wound healing in a rat model of combined radiation and wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation (10-40 Gy) was delivered to the skin without significant exposure to internal organs. At 1 h postirradiation, two skin wounds were made on the back of each rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days postirradiation. The wound areas were measured, and tissue samples were evaluated for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results clearly demonstrate that radiation exposure significantly delayed wound healing in a dose-related manner. Evaluation of irradiated and wounded skin showed decreased deposition of laminin 332 protein in the epidermal basement membrane together with an elevated expression of all three laminin 332 genes within 3 days postirradiation. The elevated laminin 332 gene expression was paralleled by an elevated gene and protein expression of MMP2, suggesting that the reduced amount of laminin 332 in irradiated skin is due to an imbalance between laminin 332 secretion and its accelerated processing by elevated tissue metalloproteinases. Western blot analysis of cultured rat keratinocytes showed decreased laminin 332 deposition by irradiated cells, and incubation of irradiated keratinocytes with MMP inhibitor significantly increased the amount of deposited laminin 332. Furthermore, irradiated keratinocytes exhibited a longer time to close an artificial wound, and this delay was partially corrected by seeding keratinocytes on laminin 332-coated plates. These data strongly suggest that laminin 332 deposition is inhibited by ionizing radiation and, in combination with slower keratinocyte migration, can contribute to the delayed wound healing of irradiated skin.
Author List
Jourdan MM, Lopez A, Olasz EB, Duncan NE, Demara M, Kittipongdaja W, Fish BL, Mäder M, Schock A, Morrow NV, Semenenko VA, Baker JE, Moulder JE, Lazarova ZAuthors
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinNatalya V. Morrow PhD Assistant Professor in the Radiation Oncology department at Medical College of Wisconsin
Edit Olasz MD, PhD Associate Professor in the Dermatology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBasement Membrane
Cell Adhesion Molecules
Cell Movement
Epidermis
Keratinocytes
Male
Matrix Metalloproteinase 2
Protein Transport
RNA, Messenger
Radiation Injuries, Experimental
Rats
Skin
Up-Regulation
Wound Healing