scholarly journals Adenosine A1 Receptor Deficiency Aggravates Extracellular Matrix Accumulation in Diabetic Nephropathy through Disturbance of Peritubular Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Dongli Tian ◽  
Jiaying Li ◽  
Linfeng Zou ◽  
Min Lin ◽  
Xiaoxiao Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Immunohistochemical Staining ◽  
Adenosine A1 Receptor ◽  
Pronounced Increase ◽  
Matrix Deposition ◽  
Adenosine A1 ◽  
Proximal Tubular ◽  
A1 Receptor

Background. We previously observed that adenosine A1 receptor (A1AR) had a protective role in proximal tubular megalin loss associated with albuminuria in diabetic nephropathy (DN). In this study, we aimed to explore the role of A1AR in the fibrosis progression of DN. Methods. We collected DN patients’ samples and established a streptozotocin-induced diabetes model in wild-type (WT) and A1AR-deficient (A1AR-/-) mice. The location and expression of CD34, PDGFRβ, and A1AR were detected in kidney tissue samples from DN patients by immunofluorescent and immunohistochemical staining. We also analyzed the expression of TGFβ, collagen (I, III, and IV), α-SMA, and PDGFRβ using immunohistochemistry in WT and A1AR-/- mice. CD34 and podoplanin expression were analyzed by Western blotting and immunohistochemical staining in mice, respectively. Human renal proximal tubular epithelial cells (HK2) were cultured in medium containing high glucose and A1AR agonist as well as antagonist. Results. In DN patients, the expression of PDGFRβ was higher with the loss of CD34. The location of PDGFRβ and TGFβ was near to each other. The A1AR, which was colocalized with CD34 partly, was also upregulated in DN patients. In WT-DN mice, obvious albuminuria and renal pathological leisure were observed. In A1AR-/- DN mice, more severe renal tubular interstitial fibrosis and more extracellular matrix deposition were observed, with lower CD34 expression and pronounced increase of PDGFRβ. In HK2 cells, high glucose stimulated the epithelial-mesenchymal transition (EMT) process, which was inhibited by A1AR agonist. Conclusion. A1AR played a critical role in protecting the tubulointerstitial fibrosis process in DN by regulation of the peritubular microenvironment.

scholarly journals Tanshinone IIA suppresses fibrosis induced by high glucose conditions in HK-2 cells via inhibition of extracellular matrix deposition, reduction of oxidative stress, and inhibition of epithelial to mesenchymal transition

2020 ◽  
Vol 19 (4) ◽  
pp. 739-744
Author(s):  
Xi Zhao ◽  
Yao-Guang Wang ◽  
Xi-kai Yang ◽  
Man Li ◽  
Shi-Jie Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Tanshinone Iia ◽  
Heme Oxygenase 1 ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Tgf Β1

Purpose: To investigate the anti-fibrotic effects of tanshinone IIA (TS) on renal tubular epithelial cells (HK-2 cells) under high glucose conditions and their related molecular mechanism(s) of action.Methods: After treatment with TS (6 μg/mL) for 24 h, the morphology of HK-2 cells stimulated by high glucose was observed under the microscope. Additionally, potential mechanisms related to the antifibrosis effects of TS were evaluated using western blotting assay and quantitative real time PCR (qRTPCR), including transforming growth factor (TGF) β1, α-smooth muscle actin (α-SMA), heme oxygenase 1 (HO-1), laminin (LN), fibronectin (FN), and E-cadherin (E-cad).Results: A high-glucose culture environment induced fibrosis of HK-2 cells, as indicated by changes in cell morphology. The anti-fibrotic effects of TS were mainly associated with a decrease in the expression levels of TGF-β1, α-SMA and LN, while the expression of E-cad increased. These resultsalso revealed that TS increased the expressions of HO-1.Conclusion: The findings suggest that TS suppresses fibrosis caused by high glucose in HK-2 cells by inhibiting extracellular matrix deposition and epithelial-mesenchymal transition and by reducing oxidative stress. Further investigations are needed to evaluate the clinical application of this compound in diabetic nephropathy. Keywords: Tanshinone IIA, Diabetic nephropathy, HK-2 cells, Fibrosis

Adenosine A1 Receptor Antagonist Up-regulates Casp3 and Stimulates Apoptosis Rate in Breast Cancer Cell Line T47D

2020 ◽  
Vol 9 (1) ◽  
pp. 14-20
Author(s):  
Mohammad Zamani Rarani ◽  
Fahimeh Zamani Rarani ◽  
Ali Valiani ◽  
Zeinolabedin Shrifian Dastjerdi ◽  
Elias Kargar Abargouei ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell Line ◽  
P53 Gene ◽  
T47d Cell ◽  
Adenosine A1 Receptor ◽  
T47d Cells ◽  
Apoptosis Rate ◽  
Adenosine A1 ◽  
T47d Cell Line ◽  
A1 Receptor

Background: Adenosine receptor family, especially A1 type is-overexpressed in breast-derived tumor cells and the P53 gene is mutant in some of these cells while the casps gene is of wild type as well. The aim of this study was to evaluate the effect of the A1 receptor function on cell programmed death or proliferation, as well as the relationship between this receptor stimulation/inhibition and caspase 3 (casp3) expression in T47D cell line that has a mutant and non-functional P53 gene. Materials and Methods: The expression of casps3 was measured by real-time polymerase chain reaction and then flow cytometery and MTT assay were used to assess the apoptotic and proliferation cell rate after the treatment of T47D cells with specific agonist N6-cyclopentyladenosine (CPA) and antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) of this receptor 24, 48, and 72 hours after treatment. Result: Our results indicated that DPCPX significantly induces apoptosis in T47D cells and the rate of survival cell after the reduction of this treatment, especially 72 hours after treatment. Finally, the expression of casp3 was up-regulated by DPCPX treatment, especially in 72 hours while CPA treatment had opposite results (P>0.05). Conclusion: In general, DPCPX could up-regulate casp3 gene expression and subsequently increase the apoptosis rate in T47D cells with casp3 expression without the P53 gene interference. Therefore, adenosine A1 receptor antagonists may be introduced as anti-cancer agents.

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