Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats
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Background: Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms. Methods: Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7. Results: VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway. Conclusions: Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.
Abstract
Background: Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms. Methods: Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7. Results: VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway. Conclusions: Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.
참고문헌 (31)
- Deluque AL, "Paricalcitol improves the angiopoietin", Tie-2 and VEGF, Nutrients, pp.2022, 14[DOI]
- Hua W, "TGFbetainduced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer", Cell Mol Life Sci, 77, pp.2103~2123 (2020)
- Meng XM, "Inflammatory processes in renal fibrosis", Nat Rev Nephrol, 10, pp.493~503 (2014)
- Jourde-Chiche N, "Endothelium structure and function in kidney health and disease", Nat Rev Nephrol, 15, pp.87~108 (2019)
- Tang PM, "Macrophages : versatile players in renal inflammation and fibrosis", Nat Rev Nephrol, 15, pp.144~158 (2019)
- Zoja C, "Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration", Nephrol Dial Transplant, 30, pp.706~712 (2015)
- Wu Q, "Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation", Biomed Pharmacother, 137, pp.111308~ (2021)
- Li W, "Total extracts of Abelmoschus manihot L. attenuates adriamycin-induced renal tubule injury via suppression of ROS-ERK1", 2-mediated NLRP3 inflammasome activation, 2019, pp.10, 567~
- Sureshbabu A, "TGF-beta signaling in the kidney : profibrotic and protective effects", Am J Physiol Renal Physiol, 310, pp.F596~F606 (2016)
- Martinez-Arias L, "Effects of calcitriol and paricalcitol on renal fibrosis in CKD", Nephrol Dial Transplant, 36, pp.793~803 (2021)
- Egido J, "The pleiotropic effects of paricalcitol : beyond bone-mineral metabolism", Nefrologia, 36, pp.10~18 (2016)
- Salanova Villanueva L, "Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente : far beyond mineral bone disease regulation", Nefrologia (Engl Ed), 40, pp.171~179 (2020)
- Oliveira BM, "Calcitriol reduces the inflammation, endothelial damage and oxidative stress in AKI caused by cisplatin", Int J Mol Sci, 23, pp.15877~ (2022)
- Deluque AL, "Effect of calcitriol on the renal microvasculature differentiation disturbances induced by AT(1)blockade during nephrogenesis in rats", Front Med (Lausanne), 7, pp.23~ (2020)
- Souza CS, "Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1", ZEB2 expressions, 2023, pp.13, 9~
- Bikle DD, "Vitamin D metabolism, mechanism of action, and clinical applications", Chem Biol, 21, pp.319~329 (2014)
- Reis NG, "Protective effect of calcitriol on rhabdomyolysis-induced acute kidney injury in rats", Sci Rep, 9, pp.7090~ (2019)
- Agarwal R, "Antiproteinuric effect of oral paricalcitol in chronic kidney disease", Kidney Int, 68, pp.2823~2828 (2005)
- Huen SC, "Macrophages in renal injury and repair", Annu Rev Physiol, 79, pp.449~469 (2017)
- Li Z, "Arginase : shedding light on the mechanisms and opportunities in cardiovascular diseases", Cell Death Discov, 8, pp.413~ (2022)
- Sui X, "p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents", Cancer Lett, 344, pp.174~179 (2014)
- Zhou Y, "Verbena attenuates adriamycin-induced renal tubular injury via inhibition of ROS-ERK1", 2-NLRP3 signal pathway, 2022, pp.2022, 7760945~
- Chung S, "Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin", PLoS One, 12, pp.e0181757~ (2017)
- de Almeida LF, "Calcitriol reduces kidney development disorders in rats provoked by losartan administration during lactation", Sci Rep, 7, pp.11472~ (2017)
- Diaz-Coranguez M, "Tight junctions in cell proliferation", Int J Mol Sci, 20, pp.5972~ (2019)
- He L, "Bradykinin potentially stimulates cell proliferation in rabbit corneal endothelial cells through the ZO‑1", ZONAB pathway, 2018, pp.42, 71~80
- Raggi C, "Dedifferentiation and aberrations of the endolysosomal compartment characterize the early stage of nephropathic cystinosis", Hum Mol Genet, 23, pp.2266~2278 (2014)
- Li X, "1, 25-dihydroxyvitamin D3 ameliorates lupus nephritis through inhibiting the NF-kappaB and MAPK signalling pathways in MRL", lpr mice, 2022, pp.23, 243~
- Wang Q, "Vitamin D inhibits COX-2 expression and inflammatory response by targeting thioesterase superfamily member 4", J Biol Chem, 289, pp.11681~11694 (2014)
- Meng XM, "TGF-beta : the master regulator of fibrosis", Nat Rev Nephrol, 12, pp.325~338 (2016)
- Mo H, "CXCR4 induces podocyte injury and proteinuria by activating beta-catenin signaling", Theranostics, 12, pp.767~781 (2022)