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Adiponectin is present in the urine in its native conformation, and specifically reduces the secretion of MCP‐1 by proximal tubular cells
Author(s) -
SHEN YVONNE Y,
HUGHES JAQUELYNE T,
CHARLESWORTH JOHN A,
KELLY JOHN J,
PEAKE PHILIP W
Publication year - 2008
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2008.00949.x
Subject(s) - adiponectin , medicine , endocrinology , monocyte , gene isoform , adenosine , adiponectin receptor 1 , protein kinase a , urine , receptor , adenosine monophosphate , kinase , biology , biochemistry , insulin , insulin resistance , gene
SUMMARY: 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.