ASC in Renal Collecting Duct Epithelial Cells Contributes to Inflammation and Injury after Unilateral Ureteral Obstruction

This study determined whether nucleotides that bind to purinergic receptors (P2R) regulate the expression or function of serum- and glucocorticoid-inducible kinase-1 (SGK1) in mouse renal inner medullar collecting duct cells (mIMCD-3). The SGK1 protein was detected by Western blotting. A significant reduction of cytosolic SGK1 expression was observed in the cells pretreated with P2R agonist adenosine 5′- O-(3-thiotriphosphate) (ATPγS), and the reduction could be reversed by P2R antagonists. This reduction was also observed in cells that were pretreated with agonists for P2R subtypes. Using ELISA, we observed a reduced SGK1 kinase activity in ATPγS-pretreated cells. This effect was reversed by P2R antagonists. Furthermore, an increase of SGK1 kinase activity in aldosterone-pretreated cells was suppressed by ATPγS. These studies demonstrate for the first time that SGK1 can be downregulated by nucleotides in renal collecting duct epithelial cells, likely via the activation of P2R, and suggest that activation of renal purinergic signaling regulates a SGK1-dependent pathway that is known to modulate ion transport in the renal collecting duct.

Download Full-text

Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction

AJP Renal Physiology ◽

10.1152/ajprenal.00266.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. F1030-F1038 ◽

Cited By ~ 43

Author(s):

Reiko Sunami ◽

Hitoshi Sugiyama ◽

Da-Hong Wang ◽

Mizuho Kobayashi ◽

Yohei Maeshima ◽

...

Keyword(s):

Epithelial Cells ◽

Ureteral Obstruction ◽

Interstitial Fibrosis ◽

Mitochondrial Pathway ◽

Protective Role ◽

Unilateral Ureteral Obstruction ◽

Tubular Epithelial Cells ◽

Wild Type ◽

Tubulointerstitial Injury ◽

Catalase Deficiency

Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) compared with wild-type mice (C3H/AnLCsaCsa). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.

Download Full-text

Faculty Opinions recommendation of Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13357214.14726566 ◽

2011 ◽

Author(s):

Hayo Castrop

Keyword(s):

Epithelial Cells ◽

Collecting Duct ◽

Tubulointerstitial Damage ◽

Renal Collecting Duct

Download Full-text

INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction

AJP Renal Physiology ◽

10.1152/ajprenal.00378.2010 ◽

2010 ◽

Vol 299 (6) ◽

pp. F1486-F1495 ◽

Cited By ~ 44

Author(s):

Jesse M. Wolstein ◽

David H. Lee ◽

Jennine Michaud ◽

Venessa Buot ◽

Beth Stefanchik ◽

...

Keyword(s):

Cell Proliferation ◽

Knockout Mice ◽

Ureteral Obstruction ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Collecting Duct ◽

Mesenchymal Cell ◽

Transforming Growth Factor Β ◽

Unilateral Ureteral Obstruction ◽

Matrix Deposition

The INK4a proteins p16INK4a and p19ARF regulate cell cycle arrest and senescence. However, the role of these proteins in controlling these processes in the normal kidney and following injury is unknown. We performed unilateral ureteral obstruction (UUO) to induce fibrosis in 2- to 3-mo-old wild-type (WT) C57/B6 and INK4a knockout mice. By quantitative RT-PCR, p16INK4a levels were increased sixfold in WT mice 7 days after UUO and p19ARF remained undetectable. Kidney sections were examined to determine levels and localization of p16INK4a, apoptosis, fibrosis, and senescent cells. INK4a knockout mice displayed mesangial cell proliferation, increased matrix deposition, and myofibroblast differentiation under normal conditions. Following UUO, INK4a knockout mice displayed 10-fold increased tubular and interstitial cell proliferation, 75% decreased collecting duct apoptosis, 2-fold greater collagen and fibronectin deposition, and no cell senescence by senescence-associated β-galactosidase staining compared with WT mice. Both INK4a knockout mesangial cells and kidney lysates from knockout mice following injury showed elevated levels of IL-6 by ELISA compared with WT samples. INK4a knockout epithelial cell cultures displayed increased mesenchymal cell markers when exposed to transforming growth factor-β. These results confirm that p16INK4a controls cell proliferation and matrix production and mitigates fibrosis following injury and suggest that the mechanism involves a role in limiting inflammation and cell proliferation.

Download Full-text

Effect of acute ureteral obstruction on terminal collecting duct function in the weanling rat

AJP Renal Physiology ◽

10.1152/ajprenal.1979.236.3.f260 ◽

1979 ◽

Vol 236 (3) ◽

pp. F260-F267 ◽

Cited By ~ 2

Author(s):

J. Buerkert ◽

D. Martin ◽

M. Head

Keyword(s):

Ureteral Obstruction ◽

Collecting Duct ◽

Terminal Segment ◽

Unilateral Ureteral Obstruction ◽

Sodium Reabsorption ◽

Loop Of Henle ◽

Acute Obstruction ◽

Reabsorptive Capacity ◽

Weanling Rats

Micropuncture techniques were employed to evaluate the effects of unilateral ureteral obstruction (UUO) of 18 h duration on the function of the terminal collecting duct in weanling rats 90-120 min following release of obstruction. In control animals and after release of UUO, water and sodium reabsorption continued along the terminal segment of the collecting duct. Fractional delivery of water (FRH2O) and sodium (FRNa) to this segment was increased after release of UUO. A significantly greater amount of the FRH2O and FRNa was reabsorbed along the terminal collecting duct following release of obstruction than in controls. Potassium was not consistently reabsorbed or secreted in either group. Following release of UUO, the osmolality of collecting duct fluid was lower than in controls, but was not different from the osmolality of fluid obtained from the bend of the loop of Henle. The results suggest that the permeability to water and the reabsorptive capacity of the collecting duct are not altered by acute obstruction.

Download Full-text