title: Prednisone inhibits the focal adhesion kinase/receptor activator of NF-κB ligand/mitogen-activated protein kinase signaling pathway in rats with adriamycin-induced nephropathy.
abstract: The aim of the present study was to investigate the mechanisms underlying the effects of prednisone on adriamycin-induced nephritic rat kidney damage via the focal adhesion kinase (FAK)/receptor activator of nuclear factor-κB ligand (RANKL)/mitogen‑activated protein kinase (MAPK) signaling pathway. An adriamycin‑induced nephritic rat model was established to investigate these mechanisms. A total of 30 healthy male Sprague‑Dawley rats were randomly assigned to the normal, model or prednisone group. Samples of urine were collected over the course of 24 h at days 7, 14, and 28, and renal cortex tissue samples were harvested at days 14, and 28 following nephritic rat model establishment. The total urinary protein content was measured by biuret colorimetry. Pathological changes in the kidney tissue samples were observed using an electron microscope. The mRNA expressions levels of FAK, RANKL, p38, extracellular signal‑regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK), and nephrin were then quantified by reverse transcription‑quantitative polymerase chain reaction. In addition, the protein expressions levels of FAK, RANKL, p38, ERK, JNK, phosphorylated (p)‑FAK, p‑ERK, and p‑JNK were quantified by western blotting. As compared with the normal group, the protein expression levels of FAK, RANKL, p-FAK, p38 and p-ERK in the model group were increased. In the prednisone group, the protein expression levels of p-ERK decreased, as compared with the normal group. In the prednisone group, the urinary protein levels, the protein expression levels of FAK, RANKL, p38, p-FAK, p-p38 and the mRNA expression levels of FAK, p38, RANKL, ERK, JNK decreased, as compared with the model group. In the prednisone group, the mRNA and protein expression levels of nephrin and the serum expression levels of RANKL increased, the serum expression levels of osteoprotegerin (OPG) were decreased, as compared with the model group. No significant changes in the protein expression levels of JNK were observed among the groups. These results suggested that prednisone is able to protect podocytes from apoptosis, and reduce urinary protein levels by inhibiting the FAK/RANKL/MAPK signaling pathway in kidney tissue samples. Serum prednisone may induce osteoporosis via the OPG/RANK/RANKL signaling pathway.
authors.affiliation: Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Minyuan
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Nephropathy, The People's Hospital of Fujian Province, Fuzhou, Fujian 350004, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Nephropathy, The People's Hospital of Fujian Province, Fuzhou, Fujian 350004, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Nephropathy, The People's Hospital of Fujian Province, Fuzhou, Fujian 350004, P.R. China.
authors.forename: Xuelan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009393:Nephritis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000097:blood; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use*; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy; D053245:RANK Ligand / Q000097:blood / Q000235:genetics; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D008565:Membrane Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; C113267:nephrin; D004317:Doxorubicin; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D020928:Mitogen-Activated Protein Kinases; D011241:Prednisone