Providing insight into why wound healing outcomes vary depending on the time of the injury, researchers report that fibroblasts - cells critical to this process - contribute to healing differently based on cues from their circadian clocks. Clinical data from the Burn Injury Database mirrors these results, they say, revealing that at nighttime, when cellular clockwork involved in wound-healing cells is not in a so-called "active circadian phase," healing times are notably longer. These insights into when healing is most efficient could be harnessed to help improve outcomes for patients undergoing invasive procedures. Disrupting natural night/day cycles has been linked to a host of diseases including cancer and diabetes, but researchers still don't know precisely how circadian clocks influence many cell types inside the body. In particular, how different cell types put their unique clockwork to work to boost their cell-specific performances is a mystery. Seeking to understand the role for biological clocks in fibroblasts (the most common cell in connective tissue), Nathaniel Hoyle and colleagues profiled the proteins in cultured fibroblasts across two complete circadian cycles. Of the 1,608 proteins they identified, 237 ebbed and flowed in abundance according to the cellular clock, and many of those cycling proteins were involved in some aspect of reorganization of the cytoskeleton - a prerequisite for cells to migrate into open wounds to repair tissues. The scientists visualized more sluggish cytoskeleton dynamics during resting phases of the circadian cycle in cultured human cells and in mouse skin, whereas wounds that occurred during the active phase closed more quickly. Retrospective analysis of historical clinical data from the Burn Injury Database revealed that human burn wounds during nighttime took roughly 60% longer to heal than those that happened during the day. The authors speculate that resetting cellular clocks prior to surgery could help maximize healing.
Science Translational Medicine