Targeting STAT3 alleviates peritoneal fibrosis by regulating glycolysis and mesothelial-mesenchymal transition
10.19405/j.cnki.issn1000-1492.2024.04.014
- VernacularTitle:靶向STAT3通过调控糖酵解及间皮间充质转分化改善腹膜透析相关腹膜纤维化
- Author:
Qilei DENG
1
,
2
;
Jiao FU
;
Nan LI
;
Mengmeng HE
;
Dake HUANG
;
Pei ZHANG
Author Information
1. 安徽医科大学第一附属医院肾脏内科,合肥 230032
2. 安徽医科大学附属阜阳医院肾脏内科,阜阳 236112
- Keywords:
STAT3;
PFKFB3;
peritoneal fibrosis;
mesothelial-mesenchymal transition;
glycolysis;
peritoneal dial-ysis;
BP-1-102
- From:
Acta Universitatis Medicinalis Anhui
2024;59(4):647-653
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.
