Sigirr deletion upregulates NF⁃ κB and is involved in the development of renal interstitial fibrosis in mice with chronic kidney disease
10.19405/j.cnki.issn1000-1492.2023.05.004
- Author:
Ziwen Tong
1
;
Deping Xu
1
;
Zhe Wang
2
;
Ping Yang
1
;
Zhenzhen Tu
1
;
Dandan Zang
3
;
Haisheng Zhou
4
Author Information
1. Dept of Biochemistry,Anhui Medical University,Hefei 230032
2. School ofBasic Medical Science , Anhui Medical University,Hefei 230032
3. Center for Scientific Research , Anhui Medical University,Hefei 230032
4. Dept ofBiochemistry,Center for Scientific Research , Anhui Medical University,Hefei 230032
- Publication Type:Journal Article
- Keywords:
Sigirr deletion;
chronic kidney disease;
renal interstitial fibrosis;
IL⁃1β;
NF⁃κB
- From:
Acta Universitatis Medicinalis Anhui
2023;58(5):724-730
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and mechanism of Sigirr deletion in chronic kidney disease complicated with renal interstitial fibrosis (CKD⁃RIF) in mice.
Methods:polymerase chain reaction (PCR) was used for identification of gene types of mice. Mice were continuously fed with the foods containing 0. 2% adenine for 12 weeks to establish the CKD⁃RIF models. Then , serum was collected to detect levels of creatinine and nitrogen when mice were killed. H&E staining was used to analyze the pathological changes of kidney tissues. Masson staining was used to observe the degree of renal fibrosis. Immunohistochemistry was used to detect the changes of the interest proteins , such as IL⁃1β , MyD88 , activated NF⁃κB , TGF⁃ β1 , E ⁃cadherin and Vimentin.
Results:Serum creatinines and urea nitrogens of mice fed with high adenine (CKD⁃RIF groups) significantly increased , compared with those of the control groups. H&E and Masson staining results showed that there were more infiltrated inflammatory cells and more critical collagen fiber deposition in the renal tissues of the Sigirr - / - mice with CKD⁃RIF. Western blot and Immunohistochemical analysis showed that the expression of IL⁃1β and its downstream MyD88 increased , and the level of phosphorylated NF⁃κB (p⁃P65) significantly increased in the renal tissues of CKD⁃RIF mice compared with the controls. And upregulation of these proteins in renal tissues of Sigirr - / - mice with CKD⁃RIF was more obvious than that of the CKD⁃RIF Sigirr + / + mice. TGF⁃ β1 , as a key cytokine involved in renal interstitial fibrosis , significantly increased ,followed by the increase of vimentin , as well as the decrease of E ⁃cadherin . The results of vimentin and cadherin E detected by Western blot were consistent with those of immunohistochemistry , and α ⁃SMA also increased significantly.
Conclusion:Adenine diet successfully induces CKD⁃RIF mice models. Sigirr deletion is beneficial to activation of the IL⁃1β mediating NF⁃κB signal pathway ,which promotes TGF⁃ β1 expression in the renal interstitiums to induce renal interstitial fibrosis.
- Full text:2024081022295327624Sigirr缺失调控NF-...性肾病小鼠发生肾间质纤维化_童子文.pdf
