A possible contribution of lipocalin-2 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis

Summary Background Lipocalin‐2 is an adipocytokine implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease. Objectives To investigate the role of lipocalin‐2 in systemic sclerosis (SSc). Materials and methods Serum lipocalin‐2 levels were determined by enzyme‐linked immunosorbent assay in 50 patients with SSc and 19 healthy subjects. Lipocalin‐2 expression was evaluated in the skin of patients with SSc and bleomycin (BLM)‐treated mice and in Fli1‐deficient endothelial cells by reverse transcriptase‐real time polymerase chain reaction, immunoblotting and/or immunohistochemistry. Results Although serum lipocalin‐2 levels were comparable between patients with SSc and healthy controls, the prevalence of scleroderma renal crisis was significantly higher in patients with SSc with elevated serum lipocalin‐2 levels than in those with normal levels. Furthermore, serum lipocalin‐2 levels inversely correlated with estimated glomerular filtration rate in patients with SSc with renal dysfunction. Among patients with SSc with normal renal function, serum lipocalin‐2 levels positively correlated with skin score in patients with diffuse cutaneous SSc with disease duration of