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- Title
Adiponectin is present in the urine in its native conformation, and specifically reduces the secretion of MCP-1 by proximal tubular cells.
- Authors
SHEN, YVONNE Y; HUGHES, JAQUELYNE T; CHARLESWORTH, JOHN A; KELLY, JOHN J; PEAKE, PHILIP W
- Abstract
Aim: To determine whether adiponectin detected in urine is present in its native form and if adiponectin receptors (AdipoR) present and functional in proximal tubular (HK-2) cells. Background: Adiponectin is a protein with anti-inflammatory, anti-atherogenic and insulin-sensitizing properties. It has previously been detected antigenically in the urine in several forms of renal disease. Methods: We compared the isoform distribution of urinary adiponectin in patients with proteinuric and non-proteinuric renal disease with that of matched controls using chromatography and enzyme-linked immunosorbent assay. We examined whether AdipoR were present in HK-2 cells by real-time reverse transcription polymerase chain reaction. Their functionality was investigated by determining the effect of recombinant adiponectin on adenosine monophosphate-activated protein kinase phosphorylation using western blotting, and on the secretion of monocyte chemotactic protein-1 and C3 using enzyme-linked immunosorbent assays. Results: Adiponectin in the urine is physiologically intact and largely present as the low molecular weight isoform. Subjects with urinary protein >150 mg/L excreted significantly more adiponectin and its high and low molecular weight isoforms than those with <150 mg/L. mRNA for AdipoR were present in HK-2 cells, with levels of mRNA for AdipoR1 being 20 times greater than those for AdipoR2. Ligation of AdipoR on proximal tubular cells increased phosphorylation of adenosine monophosphate-activated protein kinase, and downregulated the secretion of the inflammatory cytokine monocyte chemotactic protein-1, but not of C3. Conclusion: Physiologically relevant isoforms of adiponectin are present in the urine of normal subjects and those with proteinuria. In addition, functional receptors for adiponectin are present in HK-2 cells. Abnormal levels of adiponectin in the urine may therefore activate these receptors, potentially resulting in anti-inflammatory activity.
- Subjects
PROTEINS; KIDNEY diseases; ADENOSINES; PROTEIN kinases; HYPOGLYCEMIC agents; POLYMERASE chain reaction
- Publication
Nephrology, 2008, Vol 13, Issue 5, p405
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/j.1440-1797.2008.00949.x