TY - JOUR AB - 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. AD - Hebei Key Laboratory of Integrative Medicine on Liver‑Kidney Patterns, Institute of Integrative Medicine, Shijiazhuang, Hebei 050091, P.R. China Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050091, P.R. China Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita, Chiba 108‑8329, Japan AU - Liu,Ziqian AU - Zhang,Cuijuan AU - Hao,Juan AU - Chen,Gege AU - Liu,Lingjin AU - Xiong,Yunzhao AU - Chang,Yi AU - Li,Hui AU - Shimosawa,Tatsuo AU - Yang,Fan AU - Xu,Qingyou DA - 2022/10/01 DO - 10.3892/etm.2022.11560 IS - 4 JO - Exp Ther Med KW - unilateral ureteral obstruction lung fibrosis lymphangiogenesis eplerenone mineralocorticoid receptor PY - 2022 SN - 1792-0981 1792-1015 SP - 623 ST - Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis T2 - Experimental and Therapeutic Medicine TI - Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis UR - https://doi.org/10.3892/etm.2022.11560 VL - 24 ER -