Effect of a novel phosphodiesterase 5 inhibitor, CPD1, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury.
- Author:
Ao-Lu LIU
1
;
Zhuang LI
1
;
Mei-Zhi LU
2
;
Hao-Heng QIU
1
;
Zhong-Lian XIE
1
;
Xiao-Qing LIU
1
;
Allan Zi-Jian ZHAO
1
;
Yun-Ping MU
3
;
Fang-Hong LI
4
Author Information
1. The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
2. Huadu District People's Hospital of Guangzhou, Guangzhou 510800, China.
3. The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. muyunping2018@gdut.edu.cn.
4. The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. fli@gdut.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Humans;
Male;
Mice;
Rats;
Extracellular Matrix Proteins;
Fibrosis;
Kidney;
Kidney Diseases;
Phosphodiesterase 5 Inhibitors;
Plasminogen Activator Inhibitor 1
- From:
Acta Physiologica Sinica
2023;75(1):1-9
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
