Emerging roles of inflammation-mediated endothelial-mesenchymal transition in health and disease.

Endothelial-mesenchymal transition (EndoMT), a cellular differentiation process in which endothelial cells (ECs) lose their properties and differentiate into mesenchymal cells, has been observed not only during development but also in various pathological states in adults, including cancer progression and organ/tissue fibrosis. Transforming growth factor-β (TGF-β), an inflammation-related cytokine, has been shown to play central roles in the induction of EndoMT. TGF-β induces EndoMT by regulating the expression of various transcription factors, signaling molecules, and cellular components that confer ECs with mesenchymal characteristics. However, TGF-β by itself is not necessarily sufficient to induce EndoMT to promote the progression of EndoMT-related diseases to a refractory extent. In addition to TGF-β, additional activation by other inflammatory factors is often required to stabilize the progression of EndoMT. Since recent lines of evidence indicate that inflammatory signaling molecules act as enhancers of EndoMT, we summarize the roles of inflammatory factors in the induction of EndoMT and related diseases. We hope that this review will help to develop therapeutic strategies for EndoMT-related diseases by targeting inflammation-mediated EndoMT.