Objective

2

To explore the expression level of vascular noninflammatory molecule-1 (Vanin-1) in renal tissue after renal ischemia-reperfusion (I/R) injury and its relationship with the recovery of renal function.

Methods

2

Eight-week-old male BALB/c wild-type and Vanin-1 knockout mice were subjected in this study. They were randomly divided into sham operation group

I/R group

knockout group

knockout+ I/R group

with 6 mice in each group. In the I/R model groups

the bilateral renal pedicles were separated and clamped for 35 min

and then the clamp was released to restore blood flow. For the sham operation and knockout groups

only the renal pedicles were exposed without clipping. Serum

urine

and kidney tissue specimens were collected at 0

3

and 14 d after surgery to determine blood creatinine and urea nitrogen levels and urine TGF-β level. PAS staining was used to determine the severity of renal tissue damage

and immunohistochemical assay was employed to test the expression of Vanin-1 in renal tissue. After renal tub

ular epithelial cells were isolated from the kidneys of the wild-type and Vanin-1 knockout mice

the cells were primarily cultured and then passed down to the second generation. Then the cells were divided into control group

injury group

knockout group

and knockout+injury group. The cell injury was inflicted with culture condition of hypoxia (1%O

2

94%N

2

5%CO

2

) for 48 h followed by reoxygenation (5%CO

2

95% air) for 24 h to simulate

in vitro

I/R injury model. The expression of Vanin-1 and supernatant content of TGF-β were measured.

Results

2

In 3 d after I/R injury

serum creatinine and urea nitrogen levels were significantly higher (

P

<

0.05)

and PAS staining indicated obvious renal tissue damage in the I/R and knockout+I/R groups when compared the sham operation group. But there were no significant differences in the levels and the tissue damages between the I/R and knockout+I/R groups. However

on the 14th day after I/R injury

the 2 groups got the serum creatinine and urea nitrogen levels and renal tissue damage significantly recovered than the conditions on the 3rd day

but the knockout+I/R group recovered significantly faster and obtained milder renal damage (

P

<

0.05)

lower urine TGF-β level and higher Vanin-1 level when compared with the I/R group. In the

in vitro

study

the mimic I/R injury resulted in obviously increased Vanin-1 level (

P

<

0.01)

and increased TGF-β content in the supernatant (

P

<

0.05) in the renal tubular epithelial cells when compared in the cells of the knockout+I/R group.

Conclusion

2

Vanin-1 promotes the secretion of TGF-β in renal tubular epithelial cells after I/R injury

delays the recovery of renal function

and promotes the progression of acute kidney injury (AKI) to chronic kidney disease (CKD).