The Role of Sphingosine-1 Phosphate in Keloid Formation

The role of sphingosine-1 phosphate in keloid formation.

Keloid formation is one of the most frustrating problems in wound healing. The formation of keloid may involve a complex cascade of pathogenic processes, including proliferation, apoptosis, and other processes in skin-related cells, like dermal fibroblasts. The precise mechanism underlying keloid formation is complex and has not yet been established. In this study, we identified sphingolipid expressed differentially between normal skin and keloid scar tissues and examined their function in keloid formation using fibroblasts.

5 normal and 5 keloid volunteers were enrolled in this investigation. To check the expression of S1P receptor level, real time PCR, Western blotting and immunohistochemistry test done. Relationship between Rho activity, MAP kinase, S1PR and fibroblast was analyzed By Western blotting. S1P antagonist was used to analyzing connection between S1PR and amount of collagen by Western blot. Collagen level in the tissues was analyzed by immunohistochemistry and ELISA. To find a method of signaling process of keloid, MAP kinase and Rho activation pathway were tested.

Increased level of S1PR1 and S1PR2 was observed in the keloid tissues. The quantity of collagen expression increases with the concentration of S1P. When we used inhibitors to suppress S1PR1 and S1PR2 the quantity of collagen expression have decreased. MAP kinase system and Rho activity were activated in keloid samples. Expression of JNK and ERK were elevated in Western blot. Rho activity is also elevated in keloid samples.

The results of this study showed that (1) S1P was elevated in keloid scar tissue (2) S1P was markedly related with Rho activity and MAP kinase. (3) Collagen production was inhibited by S1P antagonist. These results suggest that S1P may participate in keloid formation by collagen production and can be valuable therapeutic target for keloid lesions.

Figure 1. Above is measured by real time PCR, below is measured by western blot. Expression of S1PR is elevated in keloid tissues. The level of expressed protein was measured, higher in keloid tissues.

Figure 2. (Above)The more concentrated S1P, the more collagen expression observed. (Central) Relationship of MAP kinases pathway and keloid collagen expression. Expression of JNK and ERK were elevated in keloid tissues. (Below) Elevation of Rho activity in keloid samples.