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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 PMID: 21854211 PMCID: PMC3227557

Pubmed ID

21854211

Abstract

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, M├Ąder M, Schock A, Morrow NV, Semenenko VA, Baker JE, Moulder JE, Lazarova Z

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
Natalya 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




Scopus

2-s2.0-80155161949   13 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Basement 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
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e