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Cell adhesion molecules are critical to wound healing through leukocyte recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with lower affinity, little is known about a role of PSGL-1 in wound healing. To clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/-)) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-) mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early wound healing, which was accompanied by decreased inflammatory cell infiltration and growth factor expression. By contrast, E-selectin deficiency did not affect wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound healing was similar to that of P-selectin deficiency either alone or with E-selectin blockade. However, early granulation tissue formation, late angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/-) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade. These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells.

Background Systemic sclerosis (SSc) is connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. However, the mechanism is still unknown. Recently, it is reported that cellular senescence is associated with fibrosis and its amelioration in several diseases. Senescence associated β-galactosidase (SA-β-gal) is one of the histological marker for the cellular senescence. Objectives To determine association of cellar senescence in SSc skin and fibroblast. Methods SA-β-gal expression was investigated in skin samples from SSc patients and age- and sex- matched healthy control. SA-β-gal activity was also compared in SSc patients between sclerosis lesion (forearm) and non-sclerotic lesion (upper arm). In addition, SA-β-gal expression was also investigated in fibroblasts from SSc patients and healthy control. Senescent fibroblast established by successive subculture was used for SA-β-gal staining control. Results Senescence fibroblast showed large-scaled shape and nucleus with SA-β-gal staining. SA-β-gal expression was higher in SSc skin than control. SA-β-gal activity was observed mainly in upper dermis. Furthermore, SA-β-gal expression was observed in sclerotic skin lesion of SSc patients, however, its expression was not detected in non-sclerotic lesion of SSc patients. Furthermore, fibroblast from SSc patients showed higher SA-β-gal expression than control fibroblast. Conclusions These results suggest that cellular senescence in SSc fibroblast may contribute to disease development in patients with SSc References Coppe, J.P., et al., Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol, 2008. 6(12): p. 2853-68. Jun, J.I. and L.F. Lau, Cellular senescence controls fibrosis in wound healing. Aging (Albany NY), 2010. 2(9): p. 627-31. Leontieva, O.V. and M.V. Blagosklonny, DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY), 2010. 2(12): p. 924-35. Frippiat, C., et al., Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem, 2001. 276(4): p. 2531-7. Disclosure of Interest None Declared

Serum sTREM-1 levels were elevated in dSSc patients and correlated with severity of pulmonary fibrosis, suggesting that serum sTREM-1 is a novel serological marker for the disease severity of SSc.