MP249THE EFFECT OF PANNOX INHIBITOR APX-115 ON CHRONIC RENAL INJURY IN AN EXPERIMENTAL MURINE MODEL OF UNILATERAL URETERAL OBSTRUCTION

We investigated the role of Akt1, one of the three isoforms of Akt, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). We subjected wild type and Akt1−/− mice to UUO. The Akt1 gene was silenced in vitro using short hairpin RNA delivered via a lentiviral vector in human proximal tubular cells (HK2 cells) and kidney fibroblasts (NRK-49F cells). The obstructive kidneys of Akt1−/− mice showed more severe tubulointerstitial fibrosis than those of wild type mice. The expression of fibronectin and type I collagen was significantly increased in obstructed kidneys of Akt1−/− mice compared to those of wild type mice. The important finding was that the expression of transforming growth factor β1 (TGFβ1) was significantly increased in the Akt1−/− mice compared to the wild type mice. The knockdown of Akt1 enhanced the expression of TGFβ1 in HK2 cells. Interestingly, the upregulation of TGFβ1 due to genetic knockdown of Akt1 was associated with activation of signal transducer and activator of transcript 3 (STAT3) independently of the Smad pathway in NRK-49F and HK2 cells. Immunohistochemical staining also showed that expression of phosphorylated STAT3 was more increased in Akt1−/− mice than in wild type mice after UUO. Additionally, the deletion of Akt1 led to apoptosis of the renal tubular cells in both in vivo and in vitro studies. Conclusively, these results suggest that the deletion of Akt1 may contribute to renal fibrosis via induction of the TGFβ1/STAT3 pathway in a murine model of UUO.

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Intravoxel incoherent imaging of renal fibrosis induced in a murine model of unilateral ureteral obstruction

Magnetic Resonance Imaging ◽

10.1016/j.mri.2015.07.012 ◽

2015 ◽

Vol 33 (10) ◽

pp. 1324-1328 ◽

Cited By ~ 20

Author(s):

Tiffany Hennedige ◽

Tong San Koh ◽

Septian Hartono ◽

Yet Yen Yan ◽

In Chin Song ◽

...

Keyword(s):

Murine Model ◽

Ureteral Obstruction ◽

Renal Fibrosis ◽

Unilateral Ureteral Obstruction ◽

Incoherent Imaging

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HIGH URINARY FLOW ACCELERATES RENAL INJURY IN YOUNG RATS WITH PARTIAL UNILATERAL URETERAL OBSTRUCTION

The Journal of Urology ◽

10.1097/00005392-200006000-00086 ◽

2000 ◽

pp. 1904-1907 ◽

Cited By ~ 1

Author(s):

HIEP-THIEU NGUYEN ◽

HSI-YANG WU ◽

LAURENCE S. BASKIN ◽

BARRY A. KOGAN

Keyword(s):

Renal Injury ◽

Ureteral Obstruction ◽

Unilateral Ureteral Obstruction ◽

Urinary Flow ◽

Young Rats

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HIGH URINARY FLOW ACCELERATES RENAL INJURY IN YOUNG RATS WITH PARTIAL UNILATERAL URETERAL OBSTRUCTION

The Journal of Urology ◽

10.1016/s0022-5347(05)67594-5 ◽

2000 ◽

Vol 163 (6) ◽

pp. 1904-1907 ◽

Cited By ~ 7

Author(s):

HIEP-THIEU NGUYEN ◽

HSI-YANG WU ◽

LAURENCE S. BASKIN ◽

BARRY A. KOGAN

Keyword(s):

Renal Injury ◽

Ureteral Obstruction ◽

Unilateral Ureteral Obstruction ◽

Urinary Flow ◽

Young Rats

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Adrenomedullin Increases Renal Nitric Oxide Production and Ameliorates Renal Injury in Mice With Unilateral Ureteral Obstruction

The Journal of Urology ◽

10.1016/j.juro.2009.12.002 ◽

2010 ◽

Vol 183 (4) ◽

pp. 1630-1635 ◽

Cited By ~ 7

Author(s):

Keiichi Ito ◽

Hidehiko Yoshii ◽

Takako Asano ◽

Kaori Seta ◽

Yasunori Mizuguchi ◽

...

Keyword(s):

Nitric Oxide ◽

Renal Injury ◽

Ureteral Obstruction ◽

Unilateral Ureteral Obstruction ◽

Nitric Oxide Production ◽

Oxide Production

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Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background

AJP Renal Physiology ◽

10.1152/ajprenal.00384.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. F1024-F1032 ◽

Cited By ~ 41

Author(s):

Tipu S. Puri ◽

Mohammed I. Shakaib ◽

Anthony Chang ◽

Liby Mathew ◽

Oladunni Olayinka ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Injury ◽

Ureteral Obstruction ◽

Genetic Background ◽

Renal Fibrosis ◽

Genetic Basis ◽

Cellular Responses ◽

Unilateral Ureteral Obstruction ◽

Number Of Factors

Chronic kidney disease (CKD) begins with renal injury; the progression thereafter depends upon a number of factors, including genetic background. Unilateral ureteral obstruction (UUO) is a well-described model of renal fibrosis and as such is considered a model of CKD. We used an improved reversible unilateral ureteral obstruction (rUUO) model in mice to study the strain dependence of development of CKD after obstruction-mediated injury. C57BL/6 mice developed CKD after reversal of three or more days of ureteral obstruction as assessed by blood urea nitrogen (BUN) measurements (>40 mg/dl). In contrast, BALB/c mice were resistant to CKD with up to 10 days ureteral obstruction. During rUUO, C57BL/6 mice exhibited pronounced inflammatory and intrinsic proliferative cellular responses, disruption of renal architecture, and ultimately fibrosis. By comparison, BALB/c mice had more controlled and measured extrinsic and intrinsic responses to injury with a return to normal within several weeks after release of ureteral obstruction. Our findings provide a model that allows investigation of the genetic basis of events during recovery from injury that contribute to the development of CKD.

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