The role and mechanism of urate in the development of interstitial fibrosis in chronic kidney disease
10.19405/j.cnki.issn1000-1492.2024.07.015
- Author:
Ping Yang
1
;
Deping Xu
2
;
Ziwen Tong
1
;
Qiong Chen
3
,
4
;
Ruyue Xu
1
;
Haisheng Zhou
5
Author Information
1. Dept of Biochemistry，Anhui Medical University，Hefei 230032
2. Dept of Biochemistry，Anhui Medical University，Hefei 230032；Dept of Clinical Laboratory，The Affiliated Hefei Hospital of Anhui Medical University，Hefei 230011
3. Dept of Biochemistry，Anhui Medical University，Hefei 230032；Dept of Clinical Laboratory，The Second People '
4. s Hospital of Anhui Province，Hefei 230041
5. Dept of Biochemistry，Anhui Medical University，Hefei 230032；Center Scientific Research，Anhui Medical University，Hefei 230032
- Publication Type:Journal Article
- Keywords:
urate;
hyperuricemia;
chronic kidney disease;
renal interstitial fibrosis;
epithelial-mesenchymal trans- differentiation
- From:
Acta Universitatis Medicinalis Anhui
2024;59(7):1206-1212
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the role and mechanism of urate in chronic kidney disease complicated with renal interstitial fibrosis( CKD-RIF) ．
Methods :Mice were continuously fed with a diet containing 0. 2% adenine for a duration of 9 weeks to establish mice models with CKD-RIF．By the end of the 9-week experimental periods， collected blood samples from the posterior orbital venous plexus of mice to measure renal functions and serum urate concentrations prior to euthanizing the mice．Hematoxylin-eosin ( HE) staining and periodic acid-Schiff staining (PAS) were used to investigate the pathological alternations in kidney tissues．Masson's trichrome staining was used to observe the extent of renal fibrosis．Urate staining was used to detect urate deposition in renal tissues．Western blot and immunohistochemistry were used to detect the expression of target molecules．Scratch tests were used to ex- amine the migration abilities of cells treated with different concentrations of uric acid.
Results :The kidney function analysis showed that a significant increase in the levels of serum urea nitrogen (P = 0. 006 4 ) ，creatinine (P = 0. 008 0) and urate (P = 0. 000 7) in the CKD-RIF mice compared with the normal control group．The results of HE staining and PAS staining showed a significance of renal tubule injury and infiltration of inflammatory cells in the model group．Masson' s trichrome staining showed that a marked increase in collagen deposition in the model group．The results of urate staining showed a significant presence of urate crystals in kidney tissue of the model group when compared to the control group．Animal tissue immunoblotting and immunohistochemistry analysis showed a significant increase in the expression levels of vimentin，α-SMA and TGF-β1 in the model group in comparison to the control group．Conversely，in the model group，E-cadherin levels exhibited a dramatic reduction compared to the control group．The findings from the scratching tests showed that uric acid significantly enhanced cell migration. Western blot analysis showed a dramatic increase in the expression levels of vimentin and α-SMA，while E-cadherin exhibited significant decrease in the cells subjected to uric acid treatment．
Conclusion :Urate stimulates the secre- tion of TGF-β1 by renal tubule epithelial cells and induces epithelial-mesenchymal transdifferentiation，thereby ex- acerbating renal interstitial fibrosis in CKD.
- Full text:2024091409432231341尿酸盐在慢性肾病并发肾间质纤维化中的作用及机制_杨萍.pdf
