OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis. A total of 50% of the patients died within 12 months after being diagnosed. There are no obvious clinical symptoms in the early stage of EPS, which is easy to be missed. And there are few case reports of EPS in early stage. On December 22, 2018, a 70-year-old male patient undergoing peritoneal dialysis for 17 months, who was diagnosed as EPS, was admitted to the Department of Nephrology, the Third Xiangya Hospital, Central South University. The patient's peritoneal dialysis catheter was obstructed after peritonitis. The peritoneal dialysis fluid couldn't be drain in and out of the abdominal cavity. Therefore, the laparoscopy was performed to repair the catheter. The operation in progress showed that the peritoneum was slightly thickened and the ileocecal intestinal tube was closely adhered to the parietal peritoneum where the catheter was wrapped, indicating the early stage of EPS. Peritoneal relaxation was performed. The patient's catheter was normal after adhesiolysis. He underwent hemodialysis, nutritional supporting as well as peritoneal dialysis transition, etc. The peritonitis was controlled after 10 days and the peritoneal dialysis was resumed. After discharge from hospital, the patient took moxifloxacin for 2 more weeks. We followed up the patient for 6 months. The automated peritoneal dialysis is maintained, and everything remains normal. Clinicians need to improve understanding of EPS. Early diagnosis and laparoscopic adhesiolysis is helpful to continue peritoneal dialysis treatment.
Aged ; Early Diagnosis ; Humans ; Male ; Peritoneal Dialysis/adverse effects* ; Peritoneal Fibrosis/pathology* ; Peritoneum ; Peritonitis/pathology* ; Sclerosis/pathology*

To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis.Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs., compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (all<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all<0.05)., the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF were significantly increased in HPECs of peritoneal dialysis group (all<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF (all<0.05).High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.
Animals ; Cells, Cultured ; Connective Tissue Growth Factor ; analysis ; drug effects ; Dialysis Solutions ; adverse effects ; chemistry ; pharmacology ; Gene Expression Regulation ; drug effects ; Glucose ; adverse effects ; pharmacology ; Glucose Transporter Type 1 ; analysis ; drug effects ; physiology ; Hemodiafiltration ; adverse effects ; methods ; Humans ; Male ; Peritoneal Dialysis ; adverse effects ; methods ; Peritoneal Fibrosis ; chemically induced ; genetics ; physiopathology ; Peritoneum ; chemistry ; drug effects ; pathology ; Phloretin ; Phlorhizin ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Sodium-Glucose Transporter 1 ; analysis ; drug effects ; physiology ; Transforming Growth Factor beta1 ; analysis ; drug effects ; Uremia ; chemically induced

OBJECTIVETo observe the effect of Shenshuning Recipe (SR) on the peritoneal function, accumulation of extracellular matrix (ECM), and the expression of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the peritoneal fibrosis rats.

METHODSThe peritoneal fibrosis correlating peritoneal dialysis SD rat model was induced by injecting erythromycin and peritoneal dialysate. They were randomly divided into 4 groups according to body weight, i.e., the 1.50% peritoneal dialysate group (Group B), the 1.50% peritoneal dialysate + SR group (Group C), the 4.25% peritoneal dialysate group (Group D), and the 4.25% peritoneal dialysate +SR group (Group E), 15 in each group. Besides, another 15 rats was taken as the blank control group (n = 15, Group A). SR at the daily dose of 43.93 g/kg was given to rats in Group C and E by gastrogavage, while equal volume of normal saline was given to rats in other groups by gastrogavage. The changes of glucose in the peritoneal fluid were detected. The ultra filtration volume (UF)and mass transfer of glucose (MTG) were calculated. The pathomorphological changes of the peritoneum were observed. The distribution of collagen fiber, fibroblast count, collagen I (Col I), expressions of TIMP-1 and TGF-beta1 were determined.

RESULTSAt the end of the 6th week, statistical difference was shown in UF [(-3.3 +/- 14.2) mL] and [(-2.0 +/- 10.7) mL], MTG [(18.1 +/- 0.8) mmol/kg] and [(16.1 +/- 1.2) mmol/kg], collagen fiber [(4 721.3 +/- 541.0)%] and [(6502.7 +/- 877.4)%], fibroblast [(0.087 +/- 0.010)/mm2] and [(0.131 +/- 0.042)/mm2], Col I [(187.5 +/- 36.9)%] and [(289.7 +/- 95.6)%], TIMP-1 [(2.57 +/- 0.94)%] and [(3.63 +/- 0.29)%], and TGF-beta1 [(104.0 +/- 20.7) ng/L] and [(108.2 +/- 17.5) ng/L] between Group C and Group E, when compared with the peritoneal dialysate group at the same concentration (P < 0.05, P < 0.01).

CONCLUSIONSR could postpone the development of peritoneal fibrosis in peritoneal dialysis SD rats possibly through inhibiting expressions of TGF-beta1 and TIMP-1, and hindering the over-accumulation of ECM.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Matrix ; drug effects ; Male ; Peritoneal Dialysis ; Peritoneal Fibrosis ; metabolism ; pathology ; Peritoneum ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Sclerosing mesenteritis is a rare inflammatory disease of the bowel mesentery. It produces tumor-like masses of the mesentery composed of varying degrees of fibrosis, chronic inflammation, and fat necrosis. It has been described variously as fibrosing mesenteritis, retractile mesenteritis, mesenteric Weber Christian disease, and systemic nodular panniculitis. The etiology and pathogenesis of the disease are as yet unknown, but autoimmune disorder, previous abdominal surgery, trauma, and ischemia could play a role. The clinical features include abdominal pain, vomiting, diarrhea, and constipation. Occasionally, patients with this condition may present with bowel obstruction. Rarely, It can be associated with other idiopathic inflammatory disorders such as retroperitoneal fibrosis, sclerosing cholangitis, and orbital pseudotumors. We report a case of idiopathic sclerosing mesenteritis with retroperitoneal fibrosis in a 58-year-old man.
Anti-Inflammatory Agents/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Diagnosis, Differential ; Humans ; Laparoscopy ; Male ; Middle Aged ; Panniculitis, Peritoneal/complications/*diagnosis/drug therapy ; Prednisolone/therapeutic use ; Retroperitoneal Fibrosis/complications/*diagnosis/pathology ; Tamoxifen/therapeutic use ; Tomography, X-Ray Computed

Bordetella (B) bronchiseptica is a common veterinary pathogen, but has rarely been implicated in human infections. Most patients with B. bronchiseptica infections are compromised clinically such as in patients with a malignancy, AIDS, malnutrition, or chronic renal failure. We experienced a case of relapsing peritonitis caused by B. bronchiseptica associated with continuous ambulatory peritoneal dialysis (CAPD). A 56-yr-old male, treated with CAPD due to end stage renal disease (ESRD), was admitted with complaints of abdominal pain and a turbid peritoneal dialysate. The culture of peritoneal dialysate identified B. bronchiseptica. The patient was treated with a combination of intraperitoneal antibiotics. There were two further episodes of relapsing peritonitis, although the organism was sensitive to the used antibiotics. Finally, the indwelling CAPD catheter was removed and the patient was started on hemodialysis. This is the first report of a B. bronchiseptica human infection in the Korean literature.
Anti-Bacterial Agents/pharmacology/therapeutic use ; Bordetella Infections/*diagnosis/microbiology ; Bordetella bronchiseptica/*metabolism ; Fibrosis ; Humans ; Kidney Failure/microbiology ; Male ; Middle Aged ; Peritoneal Dialysis, Continuous Ambulatory/*methods ; Peritoneum/pathology ; Peritonitis/*microbiology ; Recurrence

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.
Animals ; Connective Tissue Growth Factor ; metabolism ; Fibrosis ; physiopathology ; prevention & control ; Humans ; Kidney Failure, Chronic ; metabolism ; therapy ; Peritoneal Dialysis ; methods ; Peritoneal Dialysis, Continuous Ambulatory ; adverse effects ; Peritoneum ; pathology ; Rabbits ; Rats ; Retrospective Studies ; Tissue Adhesions ; physiopathology ; prevention & control ; Transforming Growth Factor beta ; metabolism

A growing body of evidence indicates that epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMC) may play an important role in the development and progression of peritoneal fibrosis during long-term peritoneal dialysis (PD) leading to failure of peritoneal membrane function. Here, we review our own observations and those of others on the mechanisms of EMT of HPMC and suggest potential therapeutic strategies to prevent EMT and peritoneal fibrosis during long-term PD. We found that high glucose and H2O2 as well as transforming growth factor-beta1 (TGF-beta1) induced EMT in HPMC and that high glucoseinduced EMT was blocked not only by inhibition of TGF-beta1 but also by antioxidants or inhibitors of mitogen-activated protein kinases (MAPK). Since MAPKs are downstream target molecules of reactive oxygen species (ROS), these data suggest that high glucose-induced generation of ROS and subsequent MAPK activation mediate high glucose-induced EMT in HPMC. We and others also observed that bone morphogenetic protein-7 (BMP-7) prevented EMT in HPMC. Glucose degradation products (GDP) were shown to play a role in inducing EMT. Involvement of a mammalian target of rapamycin (mTOR) in TGF-beta1-induced EMT has also been proposed in cultured HPMC. A better understanding of the precise mechanisms involved in EMT of HPMC may provide new therapeutic strategies for inhibiting peritoneal fibrosis in long-term PD patients.
Epithelial Cells/*pathology ; Fibrosis ; Humans ; Mesoderm/*pathology ; Peritoneal Dialysis/*adverse effects ; Peritoneum/*pathology

Cell Line ; Dialysis Solutions ; adverse effects ; Epithelial Cells ; metabolism ; Fibrosis ; Humans ; Peritoneal Dialysis, Continuous Ambulatory ; adverse effects ; Peritoneum ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; analysis ; RNA, Small Interfering ; pharmacology ; Transforming Growth Factor beta ; antagonists & inhibitors ; genetics ; Transforming Growth Factor beta1

OBJECTIVE: To compare different types of peritoneal fibrosis models in rats. METHODS: Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose + lipopolysaceharides (LPS) group (4.25% PDF + LPS, Group 4), high glucose + erythromycin group (4.25% PDF + lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/ Purea), glucose reabsorption (D2/D0), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy. RESULTS: The D2/D0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 (P < 0.05) . The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0. 05 ). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0.05 ). CONCLUSION Different types of peritoneal fibrosis models in rats has been established. The best model is high clusion glucose + erythromycin.
Animals ; Disease Models, Animal ; Fibrosis ; chemically induced ; etiology ; Male ; Peritoneal Dialysis ; adverse effects ; Peritoneum ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley