Newswise — Wound healing is a highly choreographed, four-act biological drama of clotting, inflammation, cell proliferation and tissue remodeling. It features an exotic cast of clotting and growth factors, specialized cells and structural proteins, each of whom must time their entrance and exit perfectly. Nothing messes up this timing like cigarette smoke. Clinical studies have consistently shown that individuals exposed to cigarette smoke—whether "first-" or "second-hand" —heal poorly and are more likely to develop fibrotic (scarring) diseases.
The negative effects of smoking on cells during the inflammatory phase of tissue repair are well documented. However the effects of cigarette smoke on the phase in which cells (fibroblasts) proliferate and migrate to create 'healing tissue', are less understood. Manuela Martins-Green of the University of California, Riverside, took a closer look. Cigarette smoke delays the formation of healing tissue and sets the stage for increased scarring, says Martins-Green, but it does so in a counter-intuitive way.
Using doses of cigarette smoke equivalent to 'first-hand' and 'second-hand' exposure in humans, Martins-Green and her colleagues focused on the structure and function of fibroblasts both in mouse models and in tissue culture. Fibroblasts secrete many proteins that compose the extracellular matrix, and are critical in orchestrating tissue repair and remodeling. Surprisingly, at doses found in tissues of smokers, smoke did not kill the fibroblasts, but instead damaged them in a way that caused them to produce stress response and survival proteins; these proteins helped the fibroblasts survive. However cell survival is the wrong process at the wrong time, in terms of forming healing tissue. During development of this tissue in normal wound healing, the fibroblasts at the site of the wound produce proteins that form a matrix into which fibroblasts and endothelial cells migrate from outside the wounded tissue. These cells then knit the healing tissue together Smoke stimulates these cells to stay alive but impairs their ability to move, causing them to build up at the margin of the wound. ..
The in vivo mouse studies and in vitro human cell culture models of wound healing both give the same results, says Martins-Green. "Taken together, our results suggest that tobacco smoke may delay wound repair because of the inability of the fibroblasts to migrate into the wounded area, leading to an accumulation of these cells at the edge of the wound, thus preventing the formation of the healing tissue. Furthermore, the smoke-induced survival of cells that should have died, coupled to the smoke-induced decrease in cell migration activity, causes a build-up of scar tissue, thereby contributing to fibrosis and excess scarring."
Says Martins-Green, "We're now trying to isolate the component or components in smoke that inhibit cell migration and block cell death."
First- and Second-Hand Cigarette Smoke Affect Cell Migration and Survival during Tissue Repair, L. S. Wong, R. L. Sielaff, H. Yuan, M. Bhattacharya, M. Zafarani, M. Martins-Green; Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA.
At the meeting: Session 140 Epithelia, Poster Presentation #587, Halls D/E. Author presents: Sunday, Dec. 5, Noon—1:30 PM.
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