INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 13
·10839
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IF 5.6
Mingkang Zhang,Ruirui Cui,Yan Zhou,Yanrong Ma,Yongwen Jin,Lina Wang,Wen Kou,Xin’an Wu
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.Keywords:hyperuricemia;renal fibrosis;mast cells;TGF-β1/Smad2/3 pathway;oxidative stress
研究领域:
肾病学
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病理生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2024
·
IF 3.2
Mingkang Zhang,Jinru Yang,Yufan Yuan,Yan Zhou,Yazhi Wang,Ruirui Cui,Yimai Maliu,Fen Xu,Xin’an Wu
Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-β1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.
研究领域:
肝病学
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药理学
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病理学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2024
·
IF 4.8
Xiaowei Zhang,Jiajun Wang,Shixie Xiang,Liang Zhao,Mingzhen Lv,Yafei Duan,Gai Gao,Pan Wang,Jenny Jie Chen,Jiangyan Xu,Zhishen Xie,Zhenqiang Zhang
Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro . The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of db/db mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF- β 1/Smad2/3 pathway in both db/db mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF- β 1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF- β 1, thereby regulating HDAC3-mediciated Klotho/TGF- β 1/Smad2/3 pathway.
研究领域:
药理学
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肾病学
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分子生物学
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糖尿病
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产品关联
DOI
PubMed
高影响因子
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