Evaluation of Klotho gene expression and NGAL levels following acute kidney injury during pregnancy hypertensive disorders

Jiang, Wenyan; Li, Yuejia; Jiang, Yuxin; Wei-nan, GU; Huang, Hongdi; Wei, Qixi; Bai, Ge; Wang, Jianhong; Rizak, Joshua D.; Zhu, Zhen

doi:10.1016/j.preghy.2022.08.008

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Fibrosis is also a major pathological alteration in kidney injury [28]. In the present study, Masson staining revealed that the area of fibrosis in the kidney tissues increased Oxidative stress also exhibits an important influence on the progression of kidney injury [25]. The DHE staining conducted in this study showed that treatment with SOP reversed the upregulation of the total superoxide level stimulated by ISO.…”

Section: Discussionsupporting

confidence: 58%

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Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

Zhou

2022

Molecules

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One of the most common diseases affecting people and leading to high morbidity is kidney injury. The alleviation of inflammation and apoptosis is considered a potential therapeutic approach for kidney injury. Sophocarpine (SOP), a tetracyclic quinolizidine alkaloid, exhibits various beneficial biological properties. To investigate the effects of SOP on isoproterenol (ISO)-induced kidney injury, we randomly divided mice into four groups: Control, ISO, ISO+SOP (20 mg/kg) and ISO+SOP (40 mg/kg). SOP was administered intraperitoneally to the mice over two weeks, accompanied by intraperitoneal stimulation of ISO (10 mg/kg) for another four weeks. After the mice were sacrificed, several methods such as ELISA, staining (H&E, TUNEL, DHE and Masson) and Western blotting were applied to detect the corresponding indicators. The kidney injury serum biomarkers SCr and BUN increased after the ISO challenge, while this effect was reversed by treatment with SOP. Pathological changes induced by ISO were also reversed by treatment with SOP in the staining. The inflammatory cytokines IL-β, IL-6, TNF-α, MCP-1 and NLRP3 increased after the challenge with ISO, while they were decreased by treatment with SOP. The apoptotic proteins cleaved-caspase-3 and Bax increased, while Bcl-2 decreased, after the challenge with ISO, and these effects were reversed by treatment with SOP. The antioxidant proteins SOD-1 and SOD-2 decreased after being stimulated by ISO, while they increased after the treatment with SOP. The fibrotic proteins collagen I, collagen III, α-SMA, fibronectin, MMP-2 and MMP-9 increased after the challenge with ISO, while they decreased after the treatment with SOP. We further discovered that the TLR-4/NF-κB and TGF-β1/Smad3 signaling pathways were suppressed, while the Nrf2/HO-1 signaling pathway was activated. In summary, SOP could alleviate ISO-induced kidney injury by inhibiting inflammation, apoptosis, oxidative stress and fibrosis. The molecular mechanisms were suppression of the TLR-4/NF-κB and TGF-β1/Smad3 signaling pathways and activation of the Nrf2/HO-1 signaling pathway, indicating that SOP might serve as a novel therapeutic strategy for kidney injury.

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Section: Discussionsupporting

confidence: 58%

“…These results reveal that treatment with SOP could attenuate ISO-induced renal apoptosis. Oxidative stress also exhibits an important influence on the progression of kidney injury [25]. The DHE staining conducted in this study showed that treatment with SOP reversed the upregulation of the total superoxide level stimulated by ISO.…”

Section: Discussionsupporting

confidence: 49%

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

Zhou

2022

Molecules

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“…the manifestation of various diseases. It has been shown that the KLOTHO gene has great potential for future therapeutic purposes in both acute and chronic kidney diseases [3][4][5]. The KLOTHO gene is highly expressed in the kidney (RPKM 80.6) and placenta (RPKM 14.7).…”

Section: Introductionmentioning

confidence: 99%

piRNAs and miRNAs Can Bind to mRNA of <i>KLOTHO</i> and <i>FGF23</i> Genes

Ivashchenko,

Akhmetova,

Zhanuzakov

et al. 2023

Preprint

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The problem of increasing life expectancy is solved with the help of many medical and social areas. It has been established that piRNAs and miRNAs can significantly modify the expression of protein-coding genes by suppressing the translation process. The aim of this work was to establish the possibility of binding piRNAs and miRNAs with mRNA of the KLOTHO and FGF23 genes, which promote health and increase life expectancy through participation in key metabolic processes. We used the MirTarget program, which determines the quantitative characteristics of complementary interactions of all piRNAs and miRNAs nucleotides with mRNA of the genes. piR-44682, piR-1940042, piR-3008660, piR-3215034, piR-6885965, piR-7980636 and one miRNA (ID00756.3p-miR) binding to the mRNA of the KLOTHO gene were found in one cluster of binding sites (BSs). piRNA-6890096 interacted with the mRNA of KLOTHO gene in a fully complementary manner using only canonical nucleotides. Among 17494 human genes, target genes interacting with five piRNAs that bind to the mRNA of KLOTHO gene were identified. mRNA of the AFF2, BCL2L11, CPT1A, DAZAP1, NDRG3, SKIDA1, WBP4, ZIC5, ZSWIM6 genes interacted with piR-3215034 and piR-6885965, which formed clusters of BSs located in 5'UTR, CDS and 3'UTR. The piR-576442, piR-1501557, piR-1845735, piR-2069834, and piR-3029987 had BSs in the mRNAs of the FGF23 gene, located only in the 3'UTR. It is proposed to use piRNAs and miRNAs as regulators of the expression of KLOTHO and FGF23 anti-aging genes.

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Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

Sabren,

Hagar,

Khateeb

et al. 2024

Pregnancy Hypertension

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Evaluation of Klotho gene expression and NGAL levels following acute kidney injury during pregnancy hypertensive disorders

Cited by 5 publications

References 20 publications

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis

piRNAs and miRNAs Can Bind to mRNA of <i>KLOTHO</i> and <i>FGF23</i> Genes

Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?

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