Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

Carrillo-López, Natalia; Panizo, Sara; Arcidiacono, Maria Vittoria; Fuente, Sandra de la; Martínez-Arias, Laura; Ottaviano, Emerenziana; Ulloa, Catalina; Ruíz-Torres, María Piedad; Rodriguez, Isabel; Cannata‐Andía, Jorge B.; Naves-Díaz, Manuel; Dusso, Adriana

doi:10.3390/nu14132589

Cited by 13 publications

(6 citation statements)

References 42 publications

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“…In our case, the specific role of VSMC VDR is assessed, clearly showing that lack of vitamin D signaling in this cell type leads to lower VC. There is also an apparent discrepancy between our results and those of Carrillo-Lopez et al 47 In their study, the authors showed that treatment of CKD mice with vitamin D induced an increase in miR-145 in the arteries. However, in their study, they administered the synthetic VDRA (vitamin D receptor agonist) paricalcitol (19-nor 1,25[OH] 2 D 2 ), whereas we use the animal form of active vitamin D (1,25D).…”

Section: Discussioncontrasting

confidence: 99%

Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a

Caus

Alonso-Montes

Fernández-Martín

et al. 2023

ATVB

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BACKGROUND: Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC. METHODS: We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used. RESULTS: CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDR wt VSMCs blunted VC and decreased OPN levels. CONCLUSIONS: Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process.

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Section: Discussioncontrasting

confidence: 99%

Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a

Caus

Alonso-Montes

Fernández-Martín

et al. 2023

ATVB

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“…On Day 3 of incubation, OCN expression in the miR-141-3p mimic group was not significantly lower than that in the mimic-NC group. This result may be related to the role of OCN as an expression marker in the late stage of osteogenesis, making 3-day incubation insufficient for the fluctuation of OCN expression during complete osteogenesis (Carrillo-López et al, 2022). DSPP is an odontoblast-specific gene, and mutations in the human.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs are comprised of a group of endogenous non‐coding small RNAs with a length of 18–25 nt, regulate gene expression following transcription, and participate in multiple physiological and pathological processes (e.g., cell proliferation, differentiation, and apoptosis) (Carrillo‐López et al, 2022; He et al, 2020; Liu et al, 2021). MiR‐141‐3p, as a member of the miR‐200 family, plays a key role in the multiple cellular process (Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

Xue

et al. 2023

Int Endodontic J

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AimThe premixed bioceramic sealer iRoot SP that is widely used clinically has been reported to kill bacterial biofilms and promote osteogenic differentiation of human stem cells from the apical papilla (hSCAPs). Although miR‐141‐3p has been substantiated to be involved in the osteogenic process, the underlying mechanisms remain unclear. The aim of this study was to investigate the role of miR‐141‐3p in osteogenic differentiation and underlying mechanisms of iRoot SP‐treated hSCAPs.MethodologyhSCAPs were extracted from tissue blocks with enzyme digestion and identified by using immunofluorescence, flow cytometry and alizarin red staining. The mRNA expression level of miR‐141‐3p in hSCPAs after culture with iRoot SP was examined by quantitative real‐time PCR (qRT‐PCR) assay. SPAG9 was identified as a downstream target gene of miR‐141‐3p by dual‐luciferase report assay. Alkaline phosphatase (ALP) staining and activity detection, alizarin red staining, calcium concentration assay, qRT‐PCR and western blot were used to estimate osteogenic differentiation ability and involved protein expression levels of the osteogenic makers and signalling pathway‐related factors in iRoot SP‐treated hSCAPs. Data were analysed by one‐way anova and post hoc Tukey's test to determine any statistical differences between the experimental groups and the control group. p < .05 was considered statistically significant.ResultsExpression of miR‐141‐3p was reduced in iRoot SP‐treated hSCAPs with the increased exposure time up to 7 days, and the western blot and qRT‐PCR results revealed that the osteogenic markers osteocalcin (OCN), osterix (OSX), runt‐related transcription factor 2 (RUNX2) and dentin sialophosphoprotein (DSPP) were inversely correlated with miR‐141‐3p. The negative regulatory relationship between miR‐141‐3p and SPAG9/ mitogen‐activated protein kinases (MAPK) signalling axis was validated in this in vitro experiments.ConclusionsThe bioceramic sealer iRoot SP promoted osteogenic differentiation of hSCAPs by inhibiting miR‐141‐3p following down‐regulated SPAG9 expression, and activated MAPK pathway. These findings proposed a novel therapeutic impact of bioceramic sealer iRoot SP inducing bone regeneration in refractory periapical periodontitis.

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“…In clinical studies, for instance, a recent study showed that obese and non-obese type 2 diabetes mellitus (T2DM) with deficiencies of vitamin D presented an up-regulation of miR-145-5p in plasma (5.91-fold) compared with those with insufficiency (4.61-fold) and sufficiency (4.29-fold) [62]. Moreover, recently, it was demonstrated that miR-145-5p is regulated by the vitamin D 3 treatment in gastric cancer cells [63] and in aortic tissue [64]. Evidence suggests that the supplementation of vitamin D 3 may induce the reduction in expression of miR-145-5p, improving asthma status.…”

Section: The Role Of Microrna-145 In Asthma and Its Modulation By Vit...mentioning

confidence: 99%

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation

Hernández-Díazcouder,

Romero-Nava,

Del-Río-Navarro

et al. 2024

Nutrients

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Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma. Evidence supports that the dysregulation of miR-21, miR-27b, miR-145, miR-146a, and miR-155 leads to disbalance of Th1/Th2 cells, inflammation, and airway remodeling, resulting in exacerbation of asthma. This review addresses how these molecular mechanisms explain the development of asthma and its exacerbation and how vitamin D3 may modulate these microRNAs to improve asthma symptoms.

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Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

Cited by 13 publications

References 42 publications

Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a

Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a

The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway

The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin D3 Supplementation

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