Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges

Cabiati, Manuela; Salvadori, Costanza; Sapio, Annalaura; Burchielli, Silvia; Carlucci, L.; Moscato, Stefania; Sabatino, Laura; Caselli, Chiara; Mattii, Letizia; Ry, Silvia Del

doi:10.1016/j.exger.2020.110879

Cited by 11 publications

(4 citation statements)

References 38 publications

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“…Several miRNAs, such as miR-29, miR-181a, and miR-222, have been shown to be differentially regulated during aging 67 , 68 . Likewise, it has been observed in DN that several miRNAs, such as MiR-122-5p, Mir-98 and MiR-136, regulate the expression of several genes involved in renal fibrosis 69 – 71 .…”

Section: Discussionmentioning

confidence: 99%

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile

Raimundo,

da Costa Aguiar Alves,

Encinas

et al. 2023

Sci Rep

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Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy—DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult—DMA—or elderly—DME and control sham adult—CSA—or control sham elderly—CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.

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Section: Discussionmentioning

confidence: 99%

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile

Raimundo,

da Costa Aguiar Alves,

Encinas

et al. 2023

Sci Rep

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“…Until now, no related literature has been found on the negative regulation of miR-665 by lncRNA GAS5 on cell senescence and aging. There is evidence that lncRNA GAS5 is associated with cell and tissue senescence through sponging miRNA (Yao et al, 2019;Cabiati et al, 2020). Among the several potential target genes of miR-665 predicted by the TargetScan software, SDC1 was reported to be associated with senescence.…”

Section: Discussionmentioning

confidence: 99%

MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1

Chen

Liang

et al. 2021

Front. Cell Dev. Biol.

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Background: Vascular aging is considered a special risk factor for cardiovascular diseases, and vascular smooth muscle cells (VSMCs) play a major role in aging-related vascular remodeling and in the pathological process of atherosclerosis. Recent research has reported that long non-coding RNA/microRNA (lncRNA/miRNA) is a critical regulator of cellular senescence. However, the role and mechanism of lncRNA GAS5/miR-665 axis in VSMC senescence remain incompletely understood.Methods: Cellular senescence was evaluated using senescence-associated β-gal activity, the NAD+/NADH ratio, and by immunofluorescence staining of γH2AX immunofluorescence. Differentially expressed miRNAs (DEMs) were identified by miRNA microarray assays and subsequently validated by quantitative real-time PCR (qRT-PCR). A dual luciferase reporter assay was conducted to confirm the binding of lncRNA GAS5 and miR-665 as well as miR-665 and syndecan 1 (SDC1). Serum levels of miR-665, lncRNA GAS5, and SDC1 in 93 subjects were detected by qRT-PCR. The participants were subdivided into control, aging, and early vascular aging (EVA) groups, and their brachial-ankle pulse wave velocity (baPWV) was measured.Results: A total of 20 overlapping DEMs were identified in young and old VSMCs via microarray analysis. MiR-665 showed a significant alteration and, therefore, was selected for further analysis. Upregulation of miR-665 was found in aging VSMCs, and downregulation of miR-665 caused an inhibition of VSMCs senescence. Subsequently, the dual luciferase reporter assay determined the binding site of miR-665 with the 3′-UTR of lncRNA GAS5 and SDC1. Increased expression of lncRNA GAS5 expression inhibited the miR-665 level and VSMC senescence. However, as shown in rescue experiment results, either miR-665 overexpression or SDC1 knockdown significantly reversed the effects of lncRNA GAS5 on VSMC senescence. Finally, compared with that of the control group, miR-665 was highly expressed in serum samples in the aging and EVA groups, especially in the EVA groups. On the contrary, serum levels of lncRNA GAS5 and SDC1 were lower in these two groups. Collectively, in the aging and EVA groups, miR-665 expression was negatively correlated with lncRNA GAS5 and SDC1 expression.Conclusion: miR-665 inhibition functions as a vital modulator of VSMC senescence by negatively regulating SDC1, which is achieved by lncRNA GAS5 that sponges miR-665. Our findings may provide a new treatment strategy for aging-related cardiovascular diseases.

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“…An increasing number of studies have confirmed that the regenerative function of the aged liver is closely related to deficient autophagy ( 136 , 138 – 141 ). Therefore, OPN has a complex dual role in the process of liver aging; it not only induces the development of age-related liver fibrosis but also delays the aging and apoptosis of hepatocytes and promotes the regeneration of hepatocytes through mechanisms such as autophagy ( 142 ). Thus, the relationship between OPN and liver aging remains a complex subject that deserves further investigation.…”

Section: Opn Is Involved In Regulating Liver Aging and Regenerationmentioning

confidence: 99%

Osteopontin - The stirring multifunctional regulatory factor in multisystem aging

Mao

Wang

et al. 2022

Front. Endocrinol.

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Osteopontin (OPN) is a multifunctional noncollagenous matrix phosphoprotein that is expressed both intracellularly and extracellularly in various tissues. As a growth regulatory protein and proinflammatory immunochemokine, OPN is involved in the pathological processes of many diseases. Recent studies have found that OPN is widely involved in the aging processes of multiple organs and tissues, such as T-cell senescence, atherosclerosis, skeletal muscle regeneration, osteoporosis, neurodegenerative changes, hematopoietic stem cell reconstruction, and retinal aging. However, the regulatory roles and mechanisms of OPN in the aging process of different tissues are not uniform, and OPN even has diverse roles in different developmental stages of the same tissue, generating uncertainty for the future study and utilization of OPN. In this review, we will summarize the regulatory role and molecular mechanism of OPN in different tissues and cells, such as the musculoskeletal system, central nervous system, cardiovascular system, liver, and eye, during senescence. We believe that a better understanding of the mechanism of OPN in the aging process will help us develop targeted and comprehensive therapeutic strategies to fight the spread of age-related diseases.

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Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges

Cited by 11 publications

References 38 publications

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile

MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1

Osteopontin - The stirring multifunctional regulatory factor in multisystem aging

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