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Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor

Dizin, Eva
Nlandu-Khodo, Stellor
Fila, Marc
Roth, Isabelle
Doucet, Alain
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Published in American Journal of Physiology - Renal Physiology. 2013, vol. 305, no. 7, p. F1053-63
Abstract Albuminuria is strongly associated with progressive kidney tubulo-interstitial damage and chronic kidney disease (CKD) progression. In proteinuric nephropathies, albumin reabsorption by the proximal tubule is saturated and the distal nephron is exposed to high concentrations of luminal albumin that may produce adverse effects. Since proximal tubular cells exposed to albuminuria exhibit a proinflammatory and profibrotic response, we assessed the effect of albuminuria in the collecting duct (CD). With the use of kidney sections and isolated cortical CDs (CCDs) from puromycin-aminonucleoside-induced nephrotic rats (PAN rats) exhibiting proteinuria, immunofluorescence microscopy revealed internalized albumin in CD cells. In these proteinuric rats, increased expression levels of cytokines and profibrotic signaling markers were detected in isolated CCDs and bands of inflammatory fibrosis could be observed around CDs. Albumin endocytosis was confirmed by FITC-albumin uptake in cultured murine CCD (mCCDcl1) cells. Exposure of mCCDcl1 cells to albumin induced NF-κB activation as assessed by luciferase reporter gene assay, nuclear translocation of NF-κB p65 subunit, and increased NF-κB target gene expression. Moreover, albuminuria-like condition results in transforming growth factor-β1 (TGF-β1) overexpression and the upregulation of profibrotic signaling markers such as Snail or vimentin via an autocrine mechanism. In mCCDcl1 cells, neutrophil gelatinase-associated lipocalin (NGAL)/lipocalin-2/24p3 receptor (24p3R) mediates albumin endocytosis as well as activation of NF-κB and TGF-β1 signaling pathways. Therefore, CD may play a key role in initiation and/or progression of inflammation and fibrosis in response to proteinuria.
Keywords Acute-Phase Proteins/physiologyAlbumins/metabolismAlbuminuria/complications/metabolism/pathologyAnimalsCell LineEndocytosis/physiologyKidney Tubules, Collecting/metabolism/pathologyLipocalins/physiologyMaleMiceNF-kappa B/metabolismNephritis/etiology/metabolismNephrosclerosis/etiology/metabolismOncogene Proteins/physiologyRatsRats, WistarTransforming Growth Factor beta1/metabolism
PMID: 23884139
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Research groups Groupe Pierre-Yves Martin (néphrologie) (30)
Insuffisance rénale chronique (941)
Laboratoire de physiologie et pathophysiologie des cellules rénales (29)
(ISO format)
DIZIN, Eva et al. Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor. In: American Journal of Physiology - Renal Physiology, 2013, vol. 305, n° 7, p. F1053-63. doi: 10.1152/ajprenal.00006.2013 https://archive-ouverte.unige.ch/unige:43594

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Deposited on : 2014-12-17

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