miR-21 Exerts Anti-proliferative and Pro-apoptotic Effects in LPS-induced WI-38 Cells via Directly Targeting TIMP3

Li, Jinxiu; Li, You; Xia, Tian; Rong, Feng-Yan

doi:10.1007/s12013-021-00987-w

Cited by 6 publications

(7 citation statements)

References 51 publications

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“…As a result, it is reasonable to expect increased miR-21 to lead to higher production of pro-inflammatory ILs. Functional in vitro experiments with mimic miR-21 elevated the levels of IL-6 and IL-1β and reduced IL-10 [ 30 ]. In this study, we did not find a relation between miR-21 expression and pro-inflammatory ILs; nevertheless, we found a negative correlation between miR-21 and anti-inflammatory IL-10 in diabetic patients, after adjusting for sex, age, and BMI ( Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients

López-Armas¹,

Yessenbekova

González-Castañeda

et al. 2022

Antioxidants

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The development of type 2 diabetes mellitus (T2DM) vascular complications (VCs) is associated with oxidative stress and chronic inflammation and can result in endothelial dysfunctions. Circulating microRNAs play an important role in epigenetic regulation of the etiology of T2DM. We studied 30 healthy volunteers, 26 T2DM patients with no complications, and 26 T2DM patients with VCs, to look for new biomarkers indicating a risk of developing VCs in T2DM patients. Peripheral blood samples were used to determine redox state, by measuring the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; and glucose-6-phosphate dehydrogenase, G6DP) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO). Additionally, inflammatory marker levels (IL-1, IL-6, IL-18, and TNF-α), c-miR-21, and c-miR-126 expression were analyzed. T2DM patients showed the highest oxidative damage with increased GSSG/GSH ratios, LPO, and AOPP levels. In both diabetic groups, we found that diminished SOD activity was accompanied by increased CAT and decreased GRd and G6PD activities. Diabetic patients presented with increased relative expression of c-miR-21 and decreased relative expression of c-miR-126. Overall, c-miR-21, SOD, CAT, and IL-6 had high predictive values for diabetes diagnoses. Finally, our data demonstrated that IL-6 exhibited predictive value for VC development in the studied population. Moreover, c-miR-21 and c-miR-126, along with GPx and AOPP levels, should be considered possible markers for VC development in future studies.

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Section: Discussionmentioning

confidence: 99%

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients

López-Armas¹,

Yessenbekova

González-Castañeda

et al. 2022

Antioxidants

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“…In spermatogonial stem cell (SSCs), transient inhibition of miR-21 increased the number of germ cells undergoing apoptosis, suggesting that it has a role in maintaining SSC self-renewal [ 14 ]. In contrast, Li et al [ 15 ] showed that miR-21 exacerbates LPS-induced lung injury and modulates inflammatory response by exerting anti-proliferative and pro-apoptotic effects in normal human fibroblast cell. Similarly, we demonstrated that miR-21-5p can inhibit Leydig cells proliferation and induce their apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Ssc-MiR-21-5p and Ssc-MiR-615 Regulates the Proliferation and Apoptosis of Leydig Cells by Targeting SOX5

Tang

Zhang

Yue

et al. 2022

Cells

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Leydig cells (LCs) are the predominant cells of androgen production, which plays key roles in spermatogenesis and maintaining male secondary sexual characteristics. Abnormal development of LCs affects androgen levels in vivo, affects fertility and may even lead to infertility. Little is known about the regulation mechanism on LCs’ development and maturation in domestic animals, especially the regulation of non-coding RNAs. In this study, we continued to dig deeper in the previous RNA-seq data of porcine LCs from our group, combined with detecting the expression profiles in different tissues and different types of cells in the testis, to screen out candidate microRNAs (miRNAs) that may affect the regulation of LCs. A total of two miRNAs, ssc-miR-21-5p and ssc-miR-615 (“ssc” is omitted below), were finally determined. After overexpression and interference of miRNAs in vitro, the effects of candidate miRNAs on the proliferation and apoptosis of TM3 (mouse Leydig cell line) were explored. The results showed that miR-21-5p led to a decrease in TM3 cell density and p53 (apoptosis related protein) expression. Meanwhile, miR-21-5p decreased EdU positive cell numbers, but increased TUNEL positive cell numbers, suggesting miR-21-5p could inhibit proliferation and promote apoptosis. Conversely, miR-615 could increase TM3 cell density. Western blot and TUNEL assay indicated miR-615 inhibited apoptosis, but had no effect on proliferation. In addition, Sox5 was identified a potential target gene of these two miRNAs by Dual-Luciferase reporter system assay. Our findings about functions of miRNAs in TM3 and the mapping of miRNAs-target gene regulatory network would provide an important basis for the further elucidation of miRNAs in regulating pig LCs.

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“…However, a previous study showed that apoptotic processes and inflammation inhibit each other (Wallach & Kovalenko, 2014), which contradicts our results. Actually, many previous reports demonstrated simultaneous apoptosis and inflammation following LPS treatment in WI‐38 cells (Li, Li, et al, 2021; Li, Xie, & Zhang, 2021; Ma et al, 2021; Wang, Zhang, & Chen, 2021; Wang, Zhang, Zhao, & Dai, 2021; Zhang, Dong, et al, 2020; Zhang, Xiang, et al, 2020; Zhou et al, 2019). The contradictory results may be due to the different cell lines used.…”

Section: Discussionmentioning

confidence: 99%

“…A previous report suggested that sinomenine could reduce the inflammation in macrophages (Zeng & Tong, 2020). Moreover, sinomenine also inhibited the inflammatory reaction in multiple disorders, such as rheumatoid arthritis, diabetes mellitus, ischemic stroke, and asthma (Bao et al, 2016; Bi et al, 2021; Li, Li, et al, 2021; Li, Xie, & Zhang, 2021; Liu et al, 2018). These studies indicated the anti‐inflammatory activity of sinomenine.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that sinomenine has anti‐tumor and anti‐inflammatory activities (Gao et al, 2019; Wang & Li, 2011). Moreover, the anti‐inflammatory role of sinomenine has been identified in multiple inflammatory conditions, such as diabetes mellitus, atherosclerosis, and osteoarthritis (Geng et al, 2021; Huang et al, 2022; Li, Li, et al, 2021; Li, Xie, & Zhang, 2021). Hence, we assumed that sinomenine may control the progression of pediatric pneumonia.…”

Section: Introductionmentioning

confidence: 99%

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Sinomenine attenuates lipopolysaccharide‐induced inflammation and apoptosis of WI‐38 cells by reducing glutathione S‐transferase M1 expression

Liu

Zhao

2022

Chem Biol Drug Des

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Pediatric pneumonia is an infectious lung disease with high morbidity and mortality. Sinomenine, an alkaloid extracted from Caulis Sinomenii, exerts anti‐inflammatory and anti‐apoptotic activities. Lipopolysaccharide (LPS) is widely used for the establishment of an inflammatory model. This research aimed to explore the influences of sinomenine on LPS‐caused inflammatory injuries in fetal lung WI‐38 cells. WI‐38 cells were treated with LPS to establish a cellular model of pediatric pneumonia. Cell viability was evaluated using CCK‐8 assay. Apoptosis was evaluated using TUNEL staining and caspase‐3 activity assays. Inflammatory cytokines and NF‐κB p65 phosphorylation levels were measured by Enzyme‐Linked Immunosorbent Assay. Glutathione S‐transferase M1 (GSTM1) expression was detected by western blotting. Results showed that LPS reduced WI‐38 cell viability, and sinomenine protected cells against LPS‐induced viability reduction. Sinomenine concentration‐dependently attenuated LPS‐induced inflammation by reducing TNF‐α, IL‐1β and MCP‐1, and increasing IL‐10 levels. Sinomenine mitigated LPS‐induced apoptosis. GSTM1 was screened by matching the targets of sinomenine and pediatric pneumonia. GSTM1 was upregulated in LPS‐treated WI‐38 cells, and this effect was attenuated after sinomenine treatment. GSTM1 was upstream of NF‐κB pathway. Overexpression of GSTM1 reversed the suppressive functions of sinomenine on LPS‐stimulated inflammation and apoptosis. Overall, sinomenine attenuates inflammation and apoptosis in WI‐38 cells stimulated by LPS via inhibiting GSTM1 expression, indicating the therapeutic potential of sinomenine in pediatric pneumonia.

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miR-21 Exerts Anti-proliferative and Pro-apoptotic Effects in LPS-induced WI-38 Cells via Directly Targeting TIMP3

Cited by 6 publications

References 51 publications

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients

Ssc-MiR-21-5p and Ssc-MiR-615 Regulates the Proliferation and Apoptosis of Leydig Cells by Targeting SOX5

Sinomenine attenuates lipopolysaccharide‐induced inflammation and apoptosis of WI‐38 cells by reducing glutathione S‐transferase M1 expression

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