Mechanism of Fuzheng Qufeng Prescription in Suppressing Epithelial-mesenchymal Transition of Podocytes in Membranous Nephropathy Rats via TGF-β1/Smad Pathway
10.13422/j.cnki.syfjx.20210403
- VernacularTitle:扶正祛风方通过TGF-β1/Smad信号通路抑制膜性肾病大鼠足细胞转分化的机制
- Author:
Xiao-yuan GUO
1
;
Ming LEI
2
;
Zi-wei SONG
3
;
Jian WANG
3
;
Xuan XIE
1
;
Qian CAI
1
;
Bao-kui WANG
1
Author Information
1. Dongfang Hospital Affiliated to Beijing University of Chinese Medicine， Beijing 100078， China
2. Beijing Rehabilitation Hospital， Capital Medical University， Beijing 100041
3. Beijing University of Chinese Medicine， Beijing 100029， China
- Publication Type:Research Article
- Keywords:
Fuzheng Qufeng prescription;
membranous nephropathy;
rats;
podocyte;
epithelial-mesenchymal transition （EMT）;
transforming growth factor-β1 （TGF-β1）/Smad signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(8):57-65
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of Fuzheng Qufeng prescription （FZQP） on transforming growth factor-β1 （TGF-β1）/Smad signaling pathway and epithelial-mesenchymal transition of podocyte in membranous nephropathy （MN） rats and to explore its molecular mechanism for podocyte protection. Method:The rats were randomly divided into normal control group （NC） and modeling group. Rats in modeling group induced by bovine serum albumin （C-BSA） were randomly divided into model group （MN）， losartan potassium group （LP， 0.05g·kg-1）， and FZQP high dose （FZQPH， 41 g·kg-1）， medium dose （FZQPM， 20.5 g·kg-1）， and low dose （FZQPL， 10.25 g·kg-1） groups. The administration lasted for 4 weeks. In week 0， 2， and 4 of administration， the levels of 24 hours urine protein （24 h-Upro） were tested. At the end of 4th week， the levels of blood urea nitrogen （BUN） and serum creatinine （SCr） were detected， and the rats in each group were sacrificed and the renal pathological morphology changes were observed by light microscope with hematoxylin-eosin （HE）， Masson and periodic acid-silver metheramine （PASM） staining. The deposition of immune complex， the thickening of glomerular basement membrane （GBM） and podocyte foot process were observed by transmission electron microscope （TEM）. The distribution and expression intensity of Desmin in renal tissues were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of TGF-β1， Smad2/3， phospho（p）-Smad2/3， Smad7 and Desmin in renal tissues were respectively detected by Western blot （WB） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with NC group， the levels of 24 h-Upro， BUN and SCr significantly increased in model group （P<0.01）， with increased deposition of immune complex， significantly thickened GBM and fusion of foot processes， significantly increased Desmin mRNA and protein expression （P<0.01） and increased TGF-β1， Smad2， and Smad3 mRNA and protein expression （P<0.05）， and decreased Smad7 mRNA and protein expression （P<0.05，P<0.01）. Compared with model group， 24 h-Upro and BUN decreased in FZQP groups and LP group （P<0.05）， levels of serum SCr in FZQPM group decreased （P<0.05）， deposition of immune complex， thickening of GBM and fusion of foot process were all alleviated in FZQP groups and LP group. Distribution of Desmin along GBM decreased in FZQPH group， FZQPM group and LP group （P<0.05）. Both mRNA and protein expression levels of TGF-β1 and p-Smad2/Smad2 in FZQPM group decreased， while mRNA and protein expression levels of Smad7 increased （P<0.05）. Both mRNA and protein expression levels of p-Smad3/Smad3 in FZQPH group decreased （P<0.05）. Both mRNA and protein expression levels of Desmin in podocyte in FZQPH group， FZQPM group and LP group decreased （P<0.05）. Conclusion:FZQP might realize podocyte protection effect in MN via suppressing EMT mediated by overactivated TGF-β1/Smad signaling pathway.
