The Role of Endothelial Mesenchymal Transformation on Infantile Hemangioma

Abstract

Objective. Infantile hemangioma (IH) is the most common infantile benign tumor derived from endothelial cells (ECs). The mechanism of IH degeneration into fibroadipose tissue is still unclear. We aimed to explore the effects of endothelial mesenchymal transformation (EndMT) on IH and explore its underlying mechanism. Methods. HemECs were treated with different concentrations of transforming growth factor-β1 (TGF-β1) as in vitro models. The CCK-8 assay was utilized to explore the effect of TGF-β1 on cell proliferation. Scratch test was conducted to determine the role of TGF-β1 in cell invasion. The influence of TGF-β1 on the E-cadherin, vimentin, N-cadherin, and LC3B expression in HemECs was detected by Western blot analysis. Expression of TGF-β1, E-cadherin, vimentin, N-cadherin, and LC3B in IH was determined by immunohistochemistry. Results. After TGF-β1 treatment, HemECs lost pebble-like morphology and presented fusiform or fibroblast-like appearance; the proliferation activity decreased significantly, endothelial cell markers decreased; interstitial markers increased, and autophagy protein expression increased. Immunohistochemical staining demonstrated higher positive expression rate of TGF-β1 and N-cadherin and poorer positive expression rate of E-cadherin related to proliferative tissues. In addition, compared with proliferative cells, the positive expression rate of E-cadherin in degenerated tissues was significantly increased, while the positive expression rate of N-cadherin was markedly reduced. Interestingly, the immunohistochemical results indicated that LC3B expression in the proliferative phase was lower than that in the regressive phase, whereas the expression of LC3B was significantly upregulated after hemangioma endothelial cells transformed into endothelial mesenchyme. Conclusion. TGF-β1 could induce EndMT in HemECs. TGF-β1 inhibited cell proliferation in a concentration-dependent manner and promoted autophagy and migration. Our investigation demonstrated that EndMT plays a significant role in the degradation of hemangioma, which provides an insight for the treatment of hemangioma.