Regeneration of fat cells from myofibroblasts during wound healing.
Plikus MV, Guerrero-Juarez CF, Ito M, Li YR, Dedhia PH, Zheng Y, Shao M, Gay DL, Ramos R, Hsi TC, Oh JW, Wang X, Ramirez A, Konopelski SE, Elzein A, Wang A, Supapannachart RJ, Lee HL, Lim CH, Nace A, Guo A, Treffeisen E, Andl T, Ramirez RN, Murad R, Offermanns S, Metzger D, Chambon P, Widgerow AD, Tuan TL, Mortazavi A, Gupta RK, Hamilton BA, Millar SE, Seale P, Pear WS, Lazar MA, Cotsarelis G.
Science. 2017 Feb 17;355(6326):748-752. doi: 10.1126/science.aai8792.
“…Scarring represents an enormous and growing medical burden in our aging population.” (Science)
Following skin injury, either the skin remains open as a wound or closes with scar formation.
Scarring is what normally allows the body to ultimately move on. Scarring in this case can be qualified as normal and no significant impairment ensues.
However scarring can be seen as pathological when there is excessive fibrosis which results in temporary hypertrophic scarring or even keloids. Scleroderma although not directly the result of injury results in excessive fibrosis and functional diasability.
All in all pathological scarring more than the skin symptoms (itch, pain, poor blood flow) results in constriction of the underlying structures and can for example reduce mobility (disability) which adds itself to aging related changes and thus interferes with healthy aging. It is easy to imagine other scar-induced problems when taking into account the location of the scar and the surrounding anatomical structures.
In this study published in Science the authors observed in mice that:
-during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic.
-In hair follicles Myofibroblast reprogramming triggered bone morphogenetic protein (BMP) signaling and then activated of adipocyte transcription factors expressed during development.
-Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation.
In human cell cultures in vitro, the authors observed that adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro.
Conclusion: Pathologic scarring could be avoided by manipulating fibroblast plasticity. Scarring could be prevented in a wound by adding BMP.
Bibliography. Insights. P694.17 FEBRUARY 2017 • VOL 355 ISSUE 6326. Science.
Article selected by Saurat JH, MD