The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin–Beck Disease Patients and Cartilage Injury Models

Zhang, Di; Zhang, Dandan; Yang, Xiaoli; Li, Qiang; Zhang, Rongqiang; Xiong, Yongmin

doi:10.1007/s12011-022-03387-0

Cited by 6 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of chronic stress to elevate the expression of CTSK is thus likely to have been involved in Notch signaling has been shown to control cell fates and signal integration in development [39]. Laboratory evidence indicates that among the Notch receptors, Notch1/ Hes1 signaling modulates not only cell proliferation but also apoptosis in the initiation and progression of tumors and cardiovascular diseases [26,40]. One of our earlier investigations demonstrated that CTSK deficiency decreased the levels of the ischemic muscle c-Notch1 protein [26].…”

Section: Discussionmentioning

confidence: 99%

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model

Jin,

Yue,

Huang

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Background Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. Methods and results Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. Conclusions CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

show abstract

Section: Discussionmentioning

confidence: 99%

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model

Jin,

Yue,

Huang

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…In this case, epiphyseal plate lesions in KBD patients can be observed, and the expression of COLII and GPX1 in chondrocytes is reduced, indicating a potential association between the observed epiphyseal plate lesions in KBD patients and decreased chondrocyte anabolism, metabolism, and antioxidant capacity ( 72 ). Additionally, Zhang et al reported a potential correlation between the reduced plasma Se levels observed in KBD patients and inadequate dietary Se intake ( 73 ). Se deficiency may be involved in the pathological process of KBD by activating the Notch/Hes1 signalling pathway, leading to excessive chondrocyte apoptosis.…”

Section: Selenium and Kashin-beck Diseasementioning

confidence: 99%

“…Se deficiency may be involved in the pathological process of KBD by activating the Notch/Hes1 signalling pathway, leading to excessive chondrocyte apoptosis. Activation of Notch/Hes1 promotes oxidative damage, while supplementation with Se can reverse this oxidative damage ( 73 ). These findings suggest that targeting the Notch/Hes1 signalling pathway may be a novel therapeutic approach for the management of KBD.…”

Section: Selenium and Kashin-beck Diseasementioning

confidence: 99%

Effects of selenium and iodine on Kashin-Beck disease: an updated review

Liu,

Luo,

Wen

et al. 2024

Front. Nutr.

View full text Add to dashboard Cite

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

show abstract

“…Some primary selenoprotein genes in mammals have central roles in Redox signaling (GPX1, GPX3, GPX4, TRXRD1, TRXRD2), Protein folding and degradation (SEP15, SELS), and metabolism (SEP1, SPS1, SPGS) [26,27]. Selenium deficiency is associated with Keshan disease [28,[28][29][30][31], muscle weakness [32], Kashin Beck [33][34][35][36][37], cardiomyopathy [38][39][40][41], and redox dysregulation [42]. In contrast, exposure to excessive amounts of selenium can lead to disorders such as selenosis, loss of hair and nails, redox dysregulation, mitochondrial dysfunction, and cell growth inhibition [43][44][45][46][47][48].…”

Section: Prevalence and Toxicity Of Metalloids 121 Seleniummentioning

confidence: 99%

Use of Microbial Consortia in Bioremediation of Metalloid Polluted Environments

et al. 2023

View full text Add to dashboard Cite

Metalloids are released into the environment due to the erosion of the rocks or anthropogenic activities, causing problems for human health in different world regions. Meanwhile, microorganisms with different mechanisms to tolerate and detoxify metalloid contaminants have an essential role in reducing risks. In this review, we first define metalloids and bioremediation methods and examine the ecology and biodiversity of microorganisms in areas contaminated with these metalloids. Then we studied the genes and proteins involved in the tolerance, transport, uptake, and reduction of these metalloids. Most of these studies focused on a single metalloid and co-contamination of multiple pollutants were poorly discussed in the literature. Furthermore, microbial communication within consortia was rarely explored. Finally, we summarized the microbial relationships between microorganisms in consortia and biofilms to remove one or more contaminants. Therefore, this review article contains valuable information about microbial consortia and their mechanisms in the bioremediation of metalloids.

show abstract

The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin–Beck Disease Patients and Cartilage Injury Models

Cited by 6 publications

References 28 publications

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model

Effects of selenium and iodine on Kashin-Beck disease: an updated review

Use of Microbial Consortia in Bioremediation of Metalloid Polluted Environments

Contact Info

Product

Resources

About