Open Access

Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis

  • Authors:
    • Ziqian Liu
    • Cuijuan Zhang
    • Juan Hao
    • Gege Chen
    • Lingjin Liu
    • Yunzhao Xiong
    • Yi Chang
    • Hui Li
    • Tatsuo Shimosawa
    • Fan Yang
    • Qingyou Xu
  • View Affiliations

  • Published online on: August 11, 2022     https://doi.org/10.3892/etm.2022.11560
  • Article Number: 623
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic kidney disease (CKD) involves progressive and irreversible loss of renal function, often causing complications and comorbidities and impairing the function of various organs. In particular, lung injury is observed not only in advanced CKD but also in early‑stage CKD. The present study investigated the potential involvement of mineralocorticoid receptors (MRs) and lymphatic vessels in lung injury using a 180‑day unilateral ureteral obstruction (UUO) model for CKD. Changes in lung associated with lymphangiogenesis and inflammatory were analyzed in UUO rats. The pathology of the lung tissue was observed by hematoxylin and eosin and Masson's staining. Detection of the expression of lymphatic vessel endothelial hyaluronic acid receptor‑1 (LYVE‑1), Podoplanin, vascular endothelial growth factor receptor‑3 (VEGFR‑3) and VEGF C to investigate lymphangiogenesis. The mRNA and protein expression levels of IL‑1β, monocyte chemotactic protein 1, tumor necrosis factor‑α, nuclear factor κB, phosphorylated serum and glucocorticoid‑induced protein kinase‑1 and MR were evaluated using western blot, reverse transcription‑quantitative PCR, immunohistochemical staining and immunofluorescence staining. In the present study, long‑term UUO caused kidney damage, which also led to lung inflammation, accompanied by lymphangiogenesis. However, treatment with eplerenone, an MR blocker, significantly reduced the severity of lung injury and lymphangiogenesis. Therefore, lymphangiogenesis contributed to lung fibrosis in UUO rats due to activation of MRs. In addition, transdifferentiation of lymphatic epithelial cells into myofibroblasts may also be involved in lung fibrosis. Collectively, these findings provided a potential mechanism for lung fibrosis in CKD and suggested that the use of eplerenone decreased kidney damage and lung fibrosis.

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October-2022
Volume 24 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Liu Z, Zhang C, Hao J, Chen G, Liu L, Xiong Y, Chang Y, Li H, Shimosawa T, Yang F, Yang F, et al: Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis. Exp Ther Med 24: 623, 2022.
APA
Liu, Z., Zhang, C., Hao, J., Chen, G., Liu, L., Xiong, Y. ... Xu, Q. (2022). Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis. Experimental and Therapeutic Medicine, 24, 623. https://doi.org/10.3892/etm.2022.11560
MLA
Liu, Z., Zhang, C., Hao, J., Chen, G., Liu, L., Xiong, Y., Chang, Y., Li, H., Shimosawa, T., Yang, F., Xu, Q."Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis". Experimental and Therapeutic Medicine 24.4 (2022): 623.
Chicago
Liu, Z., Zhang, C., Hao, J., Chen, G., Liu, L., Xiong, Y., Chang, Y., Li, H., Shimosawa, T., Yang, F., Xu, Q."Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis". Experimental and Therapeutic Medicine 24, no. 4 (2022): 623. https://doi.org/10.3892/etm.2022.11560