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The role and mechanism of CXCR4 in renal injury and fibrosis caused by calcium oxalate crystals / 中华泌尿外科杂志
Chinese Journal of Urology ; (12): 285-290, 2022.
Article in Chinese | WPRIM | ID: wpr-933213
ABSTRACT

Objective:

To investigate the role and mechanism of chemokine receptor type 4 (CXCR4) in renal injury and fibrosis caused by calcium oxalate crystals in mice.

Methods:

In June 2021, Fifteen male C57/BL6 mice were divided into control group (5 mice), model group (5 mice), and AMD3100 intervention group (5 mice) by random number table method. In model group and AMD3100 intervention group, glyoxylate (100 mg/kg) was injected intraperitoneal for 7 consecutive days for modeling. Meanwhile, the AMD3100 intervention group was also given intraperitoneal injection of AMD3100 (1 mg/kg) for 7 days. The control group was continuously injected with equal volume saline intraperitoneally. After 7 days, peripheral blood was collected from each group to determine the levels of serum urea nitrogen (BUN) and creatinine (Scr) to assess the renal function; HE, Von-Kossa, Picrosirius Red staining was also taken from the left kidney to observe the pathological changes of renal tissue. CXCR4, transforming growth factor β1 (TGF-β1) were detected by immunohistochemistry and western blot. The expression levels of PI3K/AKT pathway-related proteins were detected by western blot.

Results:

The results of biochemical indexes showed that the serum Scr [(108.03±13.56) μmol/L vs. (39.50±4.48)μmol/L, P<0.01)] and BUN[(5.66±0.48)mmol/L vs. (0.77±0.10)mmol/L, P<0.01) levels were significantly increased in model group compared with the control group. The AMD3100 intervention group was significantly lower than the model group in terms of Scr [(65.77±3.27)μmol/L vs. (108.03±13.56)μmol/L, P<0.05) and BUN [(2.97±0.44)mmol/L vs. (5.66±0.48)mmol/L, P<0.05) levels. The results of kidney pathology in mice showed that renal tubules were significantly dilated with inflammatory cell infiltration in the model group compared with the control group, and a large number of calcium oxalate crystals and collagen fibers were deposited. The extent of kidney damage, calcium oxalate crystals and collagen fibers deposition were significantly reduced in the AMD3100 intervention group compared with the model group. The results of western blotting showed that the relative expression of CXCR4(0.639±0.019 vs. 0.158±0.012, P<0.01) and TGF-β1(0.698+ 0.018 vs. 0.314+ 0.015, P<0.05) was significantly increased in the model group compared with the control group. The relative expression of CXCR4(0.322±0.231) in the AMD3100 intervention group compared with the model group (0.322±0.231 vs. 0.639±0.019, P<0.05) and TGF-β1(0.445+ 0.017 vs. 0.698+ 0.018, P<0.05) were significantly decreased. The results of immunohistochemical staining showed the trend of CXCR4 and TGF-β1 expression in each group consistent with the results of protein blotting assay. Western blotting results showed that the expression of p-PI3K (0.613±0.016 vs. 0.213±0.011, P<0.01) and p-AKT(0.149±0.013 vs. 0.047±0.014, P<0.01) was significantly increased in the model group compared with the control group. The expression of p-PI3K in the AMD3100 intervention group compared with the model group (0.292±0.020 vs. 0.613±0.016, P<0.05) and p-AKT (0.098±0.021 vs. 0.149±0.013, P<0.05)was significantly decreased.

Conclusion:

CXCR4 inhibits calcium oxalate crystal-induced kidney injury and interstitial fibrosis in mice by targeting the PI3K/AKT pathway.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Urology Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Urology Year: 2022 Type: Article