Accumulation of Renal Fibrosis in Hyperuricemia Rats Is Attributed to the Recruitment of Mast Cells, Activation of the TGF-β1/Smad2/3 Pathway, and Aggravation of Oxidative Stress
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Published:2023-06-29
Issue:13
Volume:24
Page:10839
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Zhang Mingkang12, Cui Ruirui12, Zhou Yan23, Ma Yanrong123, Jin Yongwen123, Wang Lina34, Kou Wen23, Wu Xin’an123ORCID
Affiliation:
1. School of Pharmacy, Lanzhou University, Lanzhou 730000, China 2. Engineering Research Centre of Prevention and Control for Clinical Medication Risk, Lanzhou 730000, China 3. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China 4. Department of Radiotherapy, The First Hospital of Lanzhou University, Lanzhou 730000, China
Abstract
Renal fibrosis is relentlessly progressive and irreversible, and a life-threatening risk. With the continuous intake of a high-purine diet, hyperuricemia has become a health risk factor in addition to hyperglycemia, hypertension, and hyperlipidemia. Hyperuricemia is also an independent risk factor for renal interstitial fibrosis. Numerous studies have reported that increased mast cells (MCs) are closely associated with kidney injury induced by different triggering factors. This study investigated the effect of MCs on renal injury in rats caused by hyperuricemia and the relationship between MCs and renal fibrosis. Our results reveal that hyperuricemia contributes to renal injury, with a significant increase in renal MCs, leading to renal fibrosis, mitochondrial structural disorders, and oxidative stress damage. The administration of the MCs membrane stabilizer, sodium cromoglycate (SCG), decreased the expression of SCF/c-kit, reduced the expression of α-SMA, MMP2, and inhibited the TGF-β1/Smad2/3 pathway, thereby alleviating renal fibrosis. Additionally, SCG reduced renal oxidative stress and mitigated mitochondrial structural damage by inhibiting Ang II production and increasing renal GSH, GSH-Px, and GR levels. Collectively, the recruitment of MCs, activation of the TGF-β1/Smad2/3 pathway, and Ang II production drive renal oxidative stress, ultimately promoting the progression of renal fibrosis in hyperuricemic rats.
Funder
National Natural Science Foundation of China Natural Science Foundation of Gansu Science and Technology Planning Project of Chengguan District, Lanzhou City First Hospital of Lanzhou University intramural Engineering Research Centre of Prevention and Control for Clinical Medication Risk, Gansu Province
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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