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*

Sclerosing mesenteritis is a rare benign disease with a prevalence of 0.16–3.4% and is characterized by chronic nonspecific inflammation and extensive fibrosis in the adipose tissue of the mesentery although the exact pathogenesis is still elusive. A 65-year-old woman was referred with suspicion of an abdominal mass and biliary stones on abdominal ultrasonography and CT. Bile duct stones were confirmed by endoscopic ultrasonography and successfully treated by endoscopic retrograde cholangiography with stone removal. Furthermore, a 4.7 cm conglomerated mass on small intestinal mesentery was suspected as sclerosing mesenteritis based on the features on abdominal MRI. However, because it could not be differentiated from malignancy without histologic examination, laparoscopic excisional biopsy was performed; it showed only inflammatory cells with extensive fibrosis. Therefore, the abdominal mass was confirmed as sclerosing fibrosis and the patient was followed-up without any treatments because no mass-related symptoms accompanied the findings. Six months later, abdominal CT showed no significant change in the mass. Herein, we report a rare case of incidentally found idiopathic sclerosing mesenteritis.
Adipose Tissue ; Aged ; Bile Ducts ; Biopsy ; Cholangiography ; Endosonography ; Female ; Fibrosis ; Humans ; Immunoglobulins* ; Inflammation ; Magnetic Resonance Imaging ; Mesentery ; Panniculitis, Peritoneal ; Prevalence ; Sclerosis* ; Tomography, X-Ray Computed ; Ultrasonography

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but near-fatal complication of peritoneal dialysis (PD). Despite the high mortality rate of EPS, the surgical treatment strategy of severe EPS is yet to be established.METHODS: We retrospectively analyzed outcomes of patients with EPS who underwent enterolysis for intractable EPS at Seoul National University Hospital between 2001 and 2018. EPS was diagnosed based on the clinical symptoms and radiological findings of abdominal computed tomography (CT). CT scans were scored according to an EPS scoring system that assessed peritoneal thickening and calcification as well as bowel thickening, tethering, loculation, and dilatation.RESULTS: Thirteen patients (nine males and four females; age, 48 [29–63] years) underwent enterolysis for severe EPS. PD duration (11 [6–21] years) was not associated with survival. Two patients were newly diagnosed with EPS following kidney transplantation. Five patients died of infectious complications immediately after the surgery. Eight patients survived after the first surgery; however, five of them underwent reoperation but died of persistent infection, fistula formation, or adhesive bowel obstruction. Four young (< 60 years) male patients with relatively low CT scan scores (< 13) survived for > 2 years after the first surgery. Median survival duration from EPS diagnosis was 22 (1.3–184) months and that from the first surgery was 9 (0.3–153) months.CONCLUSION: The high mortality rate of EPS suggests the importance of appropriate surgical intervention in young symptomatic male EPS patients with relatively low CT scan scores.
Adhesives ; Diagnosis ; Dilatation ; Female ; Fistula ; Humans ; Kidney Transplantation ; Korea ; Male ; Mortality ; Peritoneal Dialysis ; Peritoneal Fibrosis ; Reoperation ; Retrospective Studies ; Seoul ; Tomography, X-Ray Computed

BACKGROUND: We investigated the effects of tranilast on epithelial-to-mesenchymal transition (EMT) in an animal model and on the EMT signaling pathway in human peritoneal mesothelial cells (HPMCs).METHODS: We performed in vitro studies (cytotoxicity, cell morphology, and western blot analyses) on HPMCs from human omenta, along with in vivo studies (peritoneal membrane function and morphometric and immunohistochemical analyses) on Sprague Dawley rats. Thirty-two rats were divided into three groups: control (C) group (peritoneal dialysis [PD] catheter but not infused with dialysate), PD group (4.25% glucose-containing dialysate), and PD + tranilast group (4.25% glucose-containing dialysate along with tranilast).RESULTS: In in vitro experiments, transforming growth factor-beta 1 (TGF-β1) increased α-smooth muscle actin and Snail expression and reduced E-cadherin expression in HPMCs. TGF-β1 also reduced cell contact, induced a fibroblastoid morphology, and increased phosphorylation of Akt, Smad2, and Smad3 in HPMCs. Tranilast significantly inhibited TGF-β1-induced EMT and attenuated these morphological changes in HPMCs. In in vivo studies, after 6 weeks of experimental PD, the peritoneal membrane was significantly thicker in the PD group than in the C group. Tranilast protected against PD-induced glucose mass transfer change and histopathological changes in rats.CONCLUSION: Tranilast prevented EMT both in HPMCs triggered with TGF-β1 and in rats with PD-induced peritoneal fibrosis. Thus, tranilast may be considered a therapeutic intervention that enables long-term PD by regulating TGF-β1 signaling pathways.
Actins ; Animals ; Blotting, Western ; Cadherins ; Catheters ; Dialysis ; Epithelial-Mesenchymal Transition ; Fibrosis ; Glucose ; Humans ; In Vitro Techniques ; Membranes ; Models, Animal ; Peritoneal Dialysis ; Peritoneal Fibrosis ; Peritoneum ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Snails

BACKGROUND: Peritoneal fibrosis is the primary reason that patients with end-stage renal disease (ESRD) have to cease peritoneal dialysis. Peritonitis caused by Gram-negative bacteria such as Escherichia coli (E. coli) were on the rise. We had previously shown that matrine inhibited the formation of biofilm by E. coli. However, the role of matrine on the epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells under chronic inflammatory conditions is still unknown. METHODS: We cultured human peritoneal mesothelial cells (HPMCs) with lipopolysaccharide (LPS) to induce an environment that mimicked peritonitis and investigated whether matrine could inhibit LPS-induced EMT in these cells. In addition, we investigated the change in expression levels of the miR-29b and miR-129-5p. RESULTS: We found that 10 μg/ml of LPS induced EMT in HPMCs. Matrine inhibited LPS-induced EMT in HPMCs in a dose-dependent manner. We observed that treatment with matrine increased the expression of E-cadherin (F = 50.993, P < 0.01), and decreased the expression of alpha-smooth muscle actin (F = 32.913, P < 0.01). Furthermore, we found that LPS reduced the expression levels of miR-29b and miR-129-5P in HPMCs, while matrine promoted the expression levels of miR-29b and miR-129-5P. CONCLUSIONS Matrine could inhibit LPS-induced EMT in HPMCs and reverse LPS inhibited expressions of miR-29 b and miR-129-5P in HPMCs, ultimately reduce peritoneal fibrosis. These findings provide a potential theoretical basis for using matrine in the prevention and treatment of peritoneal fibrosis.
Actins ; metabolism ; Alkaloids ; therapeutic use ; Cadherins ; metabolism ; Cells, Cultured ; Epithelial-Mesenchymal Transition ; drug effects ; Epithelium ; drug effects ; Fibrosis ; chemically induced ; genetics ; metabolism ; Humans ; Lipopolysaccharides ; toxicity ; MicroRNAs ; metabolism ; Peritoneal Fibrosis ; drug therapy ; Quinolizines ; therapeutic use

Encapsulating peritoneal sclerosis (EPS) is a rare cause of intestinal obstruction by a thick fibrous membrane wrapping around the small intestine. It is a possible complication after liver transplantation (LT) that can be fatal. This report describes 2 cases of EPS after LT that were successfully treated with surgery, corticosteroids, tamoxifen, and mammalian target of rapamycin inhibitor. After treatment in both cases, the patients were able to start oral feeding and have been symptom free for more than 1 year. These cases suggests that for the management of EPS, surgical treatment is mandatory when the patients present with symptoms of intestinal obstruction or if there are findings suggestive of decreased mural perfusion. Surgery should be accompanied with medical treatment to prevent the relapse of EPS.
Adrenal Cortex Hormones ; Humans ; Intestinal Obstruction ; Intestine, Small ; Liver Transplantation ; Liver* ; Membranes ; Perfusion ; Peritoneal Fibrosis* ; Recurrence ; Sirolimus ; Tamoxifen ; Transplant Recipients*

Pediatric mesenteric panniculitis is an extremely rare disease of unknown etiology characterized by chronic inflammation, fat necrosis, and fibrosis in the mesenteric adipose tissue. A previously healthy 13-year-old boy was admitted because of right upper abdominal pain. An abdominal computed tomography scan revealed increased attenuation and enhancement in the left upper abdominal omental fat and anterior peritoneal wall thickening. A laparoscopic biopsy showed mesenteric panniculitis with chronic inflammation, adiponecrosis, and septal fibrosis. Serological tests for autoimmune diseases, nested polymerase chain reaction for Mycobacterium tuberculosis, and special immunohistochemical stains for malignancy were all negative. Symptomatic improvement and improved abnormal findings were achieved after an 8-month treatment with prednisolone according to a follow-up abdominal computed tomography scan. Here, we report a case of pediatric mesenteric panniculitis treated with prednisolone.
Abdominal Pain ; Adipose Tissue ; Adolescent ; Autoimmune Diseases ; Biopsy ; Child ; Coloring Agents ; Fat Necrosis ; Fibrosis ; Follow-Up Studies ; Humans ; Inflammation ; Male* ; Mycobacterium tuberculosis ; Panniculitis, Peritoneal* ; Polymerase Chain Reaction ; Prednisolone* ; Rare Diseases ; Serologic Tests

Sclerosing mesenteritis is a rare disease presenting as chronic inflammation and fibrosis of mesentery around the small and large intestine. And in most cases, it shows indolent and benign clinical course resulting in favorable prognosis. It is often diagnosed through characterized radiologic finding in abdominal examinations including computed tomography scan. However, it is important to rule out other conditions involving mesentery when diagnosing sclerosing mesenteritis. In the case of malignancy, the method of treatment and prognosis can be completely different therefore thorough examinations are essential. We herein report a 75-year-old male who suffered from frequent diarrhea and weight loss. Initially, he was diagnosed with sclerosing mesenteritis through abdominal computed tomography scan showing "misty" soft-tissue attenuation around the mesenteric vessel. However, follow up positron emission tomography scan and biopsy finding confirmed the common bile duct cancer with lymph node metastasis.
Aged ; Biopsy ; Cholangiocarcinoma* ; Common Bile Duct ; Diarrhea ; Fibrosis ; Follow-Up Studies ; Humans ; Inflammation ; Intestine, Large ; Lymph Nodes* ; Male ; Mesentery ; Methods ; Neoplasm Metastasis* ; Panniculitis ; Panniculitis, Peritoneal* ; Positron-Emission Tomography ; Prognosis ; Rare Diseases ; Weight Loss

Sclerosing mesenteritis is a rare disease presenting as chronic inflammation and fibrosis of mesentery around the small and large intestine. And in most cases, it shows indolent and benign clinical course resulting in favorable prognosis. It is often diagnosed through characterized radiologic finding in abdominal examinations including computed tomography scan. However, it is important to rule out other conditions involving mesentery when diagnosing sclerosing mesenteritis. In the case of malignancy, the method of treatment and prognosis can be completely different therefore thorough examinations are essential. We herein report a 75-year-old male who suffered from frequent diarrhea and weight loss. Initially, he was diagnosed with sclerosing mesenteritis through abdominal computed tomography scan showing "misty" soft-tissue attenuation around the mesenteric vessel. However, follow up positron emission tomography scan and biopsy finding confirmed the common bile duct cancer with lymph node metastasis.
Aged ; Biopsy ; Cholangiocarcinoma* ; Common Bile Duct ; Diarrhea ; Fibrosis ; Follow-Up Studies ; Humans ; Inflammation ; Intestine, Large ; Lymph Nodes* ; Male ; Mesentery ; Methods ; Neoplasm Metastasis* ; Panniculitis ; Panniculitis, Peritoneal* ; Positron-Emission Tomography ; Prognosis ; Rare Diseases ; Weight Loss