Specific Calcium Signal Responses in Human Keloid-Derived Fibroblasts During Cyclical Stretching: Basic Research

Background: Keloids most commonly develop in the regions where the skin is constantly stretched. Although some keloid-derived fibroblasts exhibit higher single calcium spikes than normal dermal fibroblasts during short-time cyclical stretching, the calcium signal responses to long-time stretching remain unclear.

Methods: This study compared the intracellular Ca dynamics induced by cyclical stretching stimuli between the control group (normal dermal fibroblasts) and the keloid group (keloid-derived fibroblasts). Each group was cyclically exposed to a two-dimensional stretch (10% strain). A confocal laser microscope was used to examine intracellular Ca for 30 min fluorescently. The fluorescence intensity ratio (Fluo-8H/calcein red-orange) was used to evaluate intracellular Ca concentration every 0.5 s. A calcium spike was a transient ratio increase of ≥ 20%. Receiver operating characteristic analysis was performed to determine the cutoff value of a normal calcium spike.

Results: No significant difference was observed between the keloid and control groups in the calcium signal response-positive rates (26.9% vs. 25.0%;  = 0.9). However, the calcium spike amplitudes were significantly higher in the keloid group than in the control group (1.66 vs. 1.41;  = 0.02). The cutoff value was 2.12, and 9.6% of keloid-derived fibroblasts exhibited multiple hypercalcium spikes.

Discussion: We are conducting further research based on the hypothesis that this keloid-specific subpopulation triggers the pathogenesis of keloid formation, that is, collagen overproduction, accelerated angiogenesis, and chronic inflammation.