Browsing by Author "Fongsupa S."

Filter results by typing the first few letters
Now showing 1 - 4 of 4
  • No Thumbnail Available
    ItemMetadata only
    Altenusin, a fungal metabolite, alleviates TGF-β1-induced EMT in renal proximal tubular cells and renal fibrosis in unilateral ureteral obstruction
    (2024-02-15) Thipboonchoo N.; Fongsupa S.; Sureram S.; Sa-nguansak S.; Kesornpun C.; Kittakoop P.; Soodvilai S.; Thipboonchoo N.; Mahidol University
    Renal fibrosis is a pathological feature of chronic kidney disease (CKD), progressing toward end-stage kidney disease (ESKD). The aim of this study is to investigate the therapeutic potential of altenusin, a farnesoid X receptor (FXR) agonist derived from fungi, on renal fibrosis. The effect of altenusin was determined (i) in vitro using the transforming growth factor β1 (TGF-β1)-induced epithelial to mesenchymal transition (EMT) of human renal proximal tubular cells and (ii) in vivo using mouse unilateral ureteral obstruction (UUO). The findings revealed that incubation of 10 ng/ml TGF-β1 promotes morphological change in RPTEC/TERT1 cells, a human renal proximal tubular cell line, from epithelial to fibroblast-like cells. TGF-β1 markedly increased EMT markers namely α-smooth muscle actin (α-SMA), fibronectin, and matrix metalloproteinase 9 (MMP-9), while decreased the epithelial marker E-cadherin. Co-incubation TGF-β1 with altenusin preserved the epithelial characteristics of the renal epithelial cells by antagonizing TGF-β/Smad signaling pathway, specifically a decreased phosphorylation of Smad2/3 with an increased level of Smad7. Interestingly, the antagonizing effect of altenusin does not require FXR activation. Moreover, altenusin could reverse TGF-β1-induced fibroblast-like cells to epithelial-like cells. Treatment on UUO mice with 30 mg/kg altenusin significantly reduced the expression of α-SMA, fibronectin, and collagen type 1A1 (COL1A1). The reduction in the renal fibrosis markers is correlated with the decreased phosphorylation of Smad2/3 levels but does not improve E-cadherin protein expression. Collectively, altenusin reduces EMT in human renal proximal tubular cells and renal fibrosis by antagonizing the TGF-β/Smad signaling pathway.
  • No Thumbnail Available
    ItemMetadata only
    Establishing an External Quality Assessment (EQA) Program for Urinalysis in Medical Laboratories of Thailand
    (2022-01-01) Bordeerat N.K.; Fongsupa S.; Dansethakul P.; Rungpanitch U.; Pidetcha P.; Mahidol University
    Thailand Association of Clinical Biochemists (TACB) introduced External Quality Assurance schemes (EQAs) for urinalysis (UA) using urine strips in medical laboratories of Thailand. The few available External Quality Assessment (EQA) programs on urinary microalbumin rarely include an evaluation of clinical cases. The aim of the present study was to assess a descriptive analysis of biochemical urinalysis including urine microalbumin in the Thailand laboratory practice. From January 2021 to December 2021, four surveys were organized. EQA urine samples were distributed to the participants by mail. The participants measured the UA of 2 samples quarterly and returned the results together with the information about their instruments and suggestion for the performance of the laboratory report quarterly. Moreover, summary of the situation of each laboratory performance was feedbacked by online system. Fifty-eight laboratories participated in the survey. The EQA panels included positive and negative samples. The analytical results for passed parameters of urine chemical test range from 79.3–100%. All special tests; microalbumin, creatinine, and beta-HCG showed correct result from 85.1–96.1%. The overall accuracy, specificity, and sensitivity were 92.6, 85.7, and 75,4%, respectively. The major issues were observed: the low sensitivity for the detection of low-concentration samples and the incapacity of several methods to detect the positive sample. The assessment is needed to continuously evaluate the improvement proficiency of laboratories in Thailand.
  • No Thumbnail Available
    ItemMetadata only
    Pharmacological Effects of Panduratin A on Renal Cyst Development in In Vitro and In Vivo Models of Polycystic Kidney Disease
    (2022-04-01) Tonum K.; Srimai N.; Chabang N.; Fongsupa S.; Tuchinda P.; Torres J.A.; Weimbs T.; Soodvilai S.; Mahidol University
    Renal cyst expansion in polycystic kidney disease (PKD) involves abnormalities in both cyst-lining-cell proliferation and fluid accumulation. Suppression of these processes may retard the progression of PKD. Evidence suggests that the activation of 5′ AMP-activated protein kinase (AMPK) inhibits cystic fibrosis transmembrane conductance regulator (CFTR)–mediated chloride secretion, leading to reduced progression of PKD. Here we investigated the pharmacological effects of panduratin A, a bioactive compound known as an AMPK activator, on CFTR-mediated chloride secretion and renal cyst development using in vitro and animal models of PKD. We demonstrated that AMPK was activated in immortalized human normal renal cells and autosomal dominant polycystic kidney disease (ADPKD) cells following treatment with panduratin A. Treatment with panduratin A reduced the number of renal cyst colonies corresponding with a decrease in cell proliferation and phosphorylated p70/S6K, a downstream target of mTOR signaling. Additionally, panduratin A slowed cyst expansion via inhibition of the protein expression and transport function of CFTR. In heterozygous Han:Sprague–Dawley (Cy/+) rats, an animal model of PKD, intraperitoneal administration of panduratin A (25 mg/kg BW) for 5 weeks significantly decreased the kidney weight per body weight ratios and the cystic index. Panduratin A also reduced collagen deposition in renal tissue. Intraperitoneal administration of panduratin A caused abdominal bleeding and reduced body weight. However, 25 mg/kg BW of panduratin A via oral administration in the PCK rats, another non-orthologous PKD model, showed a significant decrease in the cystic index without severe adverse effects, indicating that the route of administration is critical in preventing adverse effects while still slowing disease progression. These findings reveal that panduratin A might hold therapeutic properties for the treatment of PKD.
  • No Thumbnail Available
    ItemMetadata only
    Pinostrobin inhibits renal CFTR-mediated Cl− secretion and retards cyst growth in cell-derived cyst and polycystic kidney disease rats
    (2022-04-01) Tonum K.; Chabang N.; Fongsupa S.; Chantawarin S.; Jiarpinitnun C.; Tuchinda P.; Soodvilai S.; Mahidol University
    Cystic fibrosis transmembrane conductance regulator (CFTR) plays crucial role in renal cyst expansion via increase in fluid accumulation. Inhibition of CFTR has been proposed to retard cyst development and enlargement in polycystic kidney disease (PKD). Pinostrobin, a bioactive natural flavonoid, possesses several pharmacological effects. The present study investigated pharmacological effects of pinostrobin on CFTR-mediated Cl− secretion and renal cyst expansion in in vitro and in vivo models. Pinostrobin (10 and 50 μM) reduced number of MDCK cell-derived cyst colonies and inhibited cyst expansion via inhibition of cell proliferation and CFTR-mediated Cl− secretion. The inhibitory effect of pinostrobin was not due to the decrease in cell viability and activity of Na+-K+-ATPase. We also investigated the natural analogue pinocembrin as well as the synthetic analogue pinostrobin oxime. Both pinocembrin and pinostrobin oxime did not reduce CFTR-mediated Cl− secretion. In PKD rats, oral administration of pinostrobin (40 mg/kg/day) exhibited a decreasing in cystic area compared to vehicle-treated rats. Pinostrobin treatment inhibited renal expression of CFTR protein in PKD rats. Our findings highlighted the potential therapeutic application of pinostrobin in PKD.