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Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients

  • Authors:
    • Deng He
    • Shaogang Wang
    • Zhaohui Jia
    • Lei Cui
    • Yuchao Lu
    • Henglong Hu
    • Baolong Qin

  • View Affiliations

  • Published online on: November 13, 2014     https://doi.org/10.3892/mmr.2014.2941
  • Pages: 2199-2206
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Abstract

The present study aimed to identify the characteristics and cross‑talk between transforming growth factor β1 (TGF‑β1) and calcium ions in nephrolithiasis patients with idiopathic hypercalciuria (IH) in order to elucidate the potential mechanisms underlying changes in cell phenotype induced by bone‑associated factors and their influence on renal nephrolithiasis formation. Blood samples from a total of 29 nephrolithiasis patients with IH, 29 renal stone patients without IH and 29 healthy age‑matched normal controls were subjected to quantification of peripheral serum TGF‑β1, osteopontin (OPN) and bone morphogenetic protein 2 (BMP2) using ELISA. This was followed by detection of BMP2, OPN and 1,25‑dihydroxyvitamin D3 receptor (VDR) mRNA and protein levels in primary renal epithelial cells (PRECs) of IH and HK‑2 human proximal tubular cell lines (control) using reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. The mRNA expression levels of BMP2, OPN and VDR in PRECs and HK‑2 were evaluated following stimulation with various concentrations of TGF‑β1 (0.5, 2.0 and 5.0 ng/ml), Ca2+ (0.5, 1.5 and 2.5 mM) or TGF‑β1 and Ca2+ combined using RT‑qPCR, respectively. TGF‑β1, BMP2 and OPN expression levels in patients with IH were all significantly higher than those in the control group. The mRNA and protein expression levels of BMP2 and VDR were significantly higher in PRECs than those in HK‑2 cells. Following incubation with TGF‑β1 and/or Ca2+, the mRNA expression levels of BMP2, OPN and VDR in PRECs increased in a dose‑dependent manner; however, no significant differences were observed in HK‑2 cells with increasing TGF‑β1 dosage. Co‑incubation with TGF‑β1 and Ca2+ in PRECs and HK‑2 cell lines resulted in similar effects and the expression of BMP2, OPN and VDR mRNA increased in a time‑dependent manner. In conclusion, the results of the present study demonstrated that TGF‑β1 regulated the expression of BMP2, OPN and VDR in PRECs, but not in HK‑2 cells. Co‑incubation with TGF‑β1 and Ca2+ significantly increased the expression levels of bone‑associated factors in PRECs and HK‑2 cells, which suggested that this process may be partially responsible for the pathogenesis of calcium stone development, and also associated with bone formation and the TGF‑β1‑induced epithelial to mesenchymal transition.
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  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
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  • CiteScore: 6.9
  • CiteScore Rank: Q2: #98/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.721
  • SCImago Journal Rank (SJR): 0.65
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Spandidos Publications style
He D, Wang S, Jia Z, Cui L, Lu Y, Hu H and Qin B: Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients. Mol Med Rep 11: 2199-2206, 2015
APA
He, D., Wang, S., Jia, Z., Cui, L., Lu, Y., Hu, H., & Qin, B. (2015). Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients. Molecular Medicine Reports, 11, 2199-2206. https://doi.org/10.3892/mmr.2014.2941
MLA
He, D., Wang, S., Jia, Z., Cui, L., Lu, Y., Hu, H., Qin, B."Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients". Molecular Medicine Reports 11.3 (2015): 2199-2206.
Chicago
He, D., Wang, S., Jia, Z., Cui, L., Lu, Y., Hu, H., Qin, B."Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients". Molecular Medicine Reports 11, no. 3 (2015): 2199-2206. https://doi.org/10.3892/mmr.2014.2941