To scar or heal? How cells decide
After an injury, cells at the border of the wound begin to rebuild new tissue and sometimes scar. New research reveals how cells switch from repair to scarring processes.
Getting a scar after a nick, scrape, or deep cut seems like just a regular part of wound healing. But scarring sometimes takes over the healing process, creating damaged inflexible tissue where healthy tissue should be. Scientists at Jefferson (Philadelphia University + Thomas Jefferson University) revealed how cells decide whether to heal or scar abnormally.
To find out why some injuries scar and others heal normally, Sue Menko, PhD, a professor and vice chair of the Department of Pathology, Anatomy and Cell biology at Jefferson, and her research team performed mock cataract surgery on tissue in a petri dish. Equipped with powerful microscopes and fluorescent tags, the scientists watched the cells begin the post-surgical repair process.
When an injury, like the mock cataract surgery picture above (left panel), damages the epithelial tissue, which makes up the outer layer of cells lining our body and our organs, repair cells capable of mending the wound rush to the injury site to start fixing things up.
While the repair cells are on the move, the injury spurs other cells to secrete a factor called vimentin that helps patch up wounds. Together with first author Janice Walker, PhD, Dr. Menko and colleagues discovered vimentin links up with the repair cells along the damaged wound border, pictured here as whiter shades at the edges of the cells (right panel). There, vimentin decides whether a wound will scar or heal—and it all depends on one thing.
The cellular environment– the tissue and cells immediately surrounding the wound -- are what determines whether an injury will heal or scar, Menko and team reported online this month in the journal Molecular Biology of the Cell. A stiff cell environment, in which cells were grown on a stiffer gel surface, encouraged repair cells to become myofibroblasts (marked in green), cells that set the stage for unhealthy scarring and fibrosis (left panel). A soft cellular environment, in contrast, prevented that from happening (right panel).
But how does a rigid environment encourage repair cells to become myofibroblasts? Dr. Menko’s research suggests vimentin may help relay a message to repair cells about the environment. In healthy environments, vimentin (shown in green in image below) incorporates into the cell’s skeleton and facilitates healing. But in stiff environments, including ones characteristic of fibrotic tissue, stress fibers (red) develop and vimentin accumulates at the very tips of cells and in the extracellular space. This soluble form of vimentin may signal repair cells to change their fate to a cell type that produces scarring/ fibrosis that impairs tissue function, and in the eye, can lead to blindness.
Article reference: J. L. Walker, B. M. Bleaken, A. R. Romisher, A. A. Alnwibit, and A. S. Menko, “In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype,” DOI: 10.1091/mbc.E17-06-0364, 2018.
-- Article by Roni Dengler
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