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A possible contribution of lipocalin-2 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis.
- Source :
- British Journal of Dermatology; Sep2015, Vol. 173 Issue 3, p681-689, 9p
- Publication Year :
- 2015
-
Abstract
- 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 < 3 years and inversely correlated with estimated right ventricular systolic pressure in total patients with SSc. Importantly, in SSc lesional skin, lipocalin-2 expression was increased in dermal fibroblasts and endothelial cells. In BLM-treated mice, lipocalin-2 was highly expressed in dermal fibroblasts, but not in endothelial cells. On the other hand, the deficiency of transcription factor Fli1, which is implicated in SSc vasculopathy, induced lipocalin-2 expression in cultivated endothelial cells. Conclusions Lipocalin-2 may be involved in renal dysfunction and dermal fibrosis of SSc. Dysregulated matrix metalloproteinase-9/lipocalin-2-dependent angiogenesis due to Fli1 deficiency may contribute to the development of pulmonary arterial hypertension associated with SSc. [ABSTRACT FROM AUTHOR]
- Subjects :
- ADIPOKINES
APOPTOSIS
KIDNEY diseases
ENZYME-linked immunosorbent assay
LIPOCALIN-2
Subjects
Details
- Language :
- English
- ISSN :
- 00070963
- Volume :
- 173
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- British Journal of Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 109927182
- Full Text :
- https://doi.org/10.1111/bjd.13779