All-trans retinoic acid enhances in vitro mesenchymal stem cells migration by targeting matrix metalloproteinases 2 and 9

Pourjafar, Mona; Saidijam, Massoud; Etemadi, Katayoon; Najafi, Rezvan

doi:10.1007/s10529-017-2350-1

Cited by 16 publications

(15 citation statements)

References 14 publications

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“…They further demonstrate the ability to increase cellular viability and counteract the inflammatory process evoked by the lipopolysaccharide mediate TLR4 activation . Stem/progenitor cells migration could be stimulated via Vitamin A, with increased expression and activity of matrix metalloproteinases‐2/‐9, inhibition of caspase‐3 enzyme activity and a biphasic effect, with the ability to drive cellular differentiation or de‐differentiation processes.…”

Section: Discussionmentioning

confidence: 88%

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

El‐Sayed

Hein

Dörfer

2019

J of Periodontal Research

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Background and objective Inflammatory cytokines impact the course of periodontal disease, repair, and regeneration. Vitamin A and its metabolites are inflammation‐modulatory biomolecules, affecting cellular pluripotency. The aim of this study was to investigate the effect of retinol and periodontal inflammatory cytokines (IL‐1β/TNF‐α/IFN‐γ) on pluripotency and proliferative properties of gingival mesenchymal stem/progenitor cells (G‐MSCs), for the first time. Material and methods Human G‐MSCs (n = 5) were STRO‐1 immuno‐magnetically sorted, characterized and expanded in basic medium (control group), in basic medium with IL‐1β (1 ng/mL), TNF‐α (10 ng/mL), and IFN‐γ (100 ng/mL) (inflammatory group), in basic medium with retinol (20 μmol/L) (retinol group) and with retinol added to the inflammatory group (inflammatory/retinol group). β‐catenin levels at 1 hour, cellular proliferation over 14 days, and colony‐forming units (CFUs) at 14 days were investigated. Pluripotency gene expressions were examined at 1, 3, and 5 days via reverse transcription‐polymerase chain reaction (RT‐PCR). Multilineage differentiation potential was evaluated, following 5 days priming, using qualitative and quantitative histochemistry and RT‐PCR. Results G‐MSCs were CD14−, CD34−, CD45−, CD73+, CD90+, CD105+, and showed mesenchymal stem/progenitor cells’ hallmarks, CFUs, and multilineage differentiation potential. Intracellular β‐catenin significantly declined in the stimulated groups (P < 0.001, Friedman test). Cellular proliferation at 72 hours was most prominent in the control and inflammatory group [Median cell numbers (Q25/Q75); 6806 (4983/7312) and 5414 (4457/7230), respectively], followed by an upsurge in the retinol group. At 14 days, the retinol group exhibited the highest CFUs [Median CFUs (Q25/Q75); 35 (20/58), P = 0.043, Wilcoxon signed‐rank]. Nanog was most expressed in the inflammatory and retinol group [Median gene expression/PGK1 (Q25/Q75); 0.0006 (0.0002/0.0014) and 0.0005 (0.0003/0.0008)]. Inflammation significantly upregulated Sox2 expression [0.0002 (0.0008/0.0005)], while its expression was diminished in the retinol and inflammatory/retinol group (P < 0.001, Friedman test). Inflammatory/retinol group exhibited the highest multilineage differentiation potential. Conclusion Controlled short‐term inflammatory/retinol stimuli activate the Wnt/β‐catenin pathway, affecting G‐MSCs’ pluripotency, proliferation, and differentiation. The present findings provide further insights into the inflammatory‐regenerative interactions and their modulation potential for G‐MSCs‐mediated periodontal repair/regeneration.

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Section: Discussionmentioning

confidence: 88%

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

El‐Sayed

Hein

Dörfer

2019

J of Periodontal Research

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“…Once such regulation becomes imbalanced, many diseases and pathological changes will be caused. This phenomenon plays an extremely important role in the occurrence and development of EM, and MMP-2 has an important relation with EM, providing a new idea and direction for the treatment of EM (27). …”

Section: Discussionmentioning

confidence: 99%

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

Sui

Sun

et al. 2018

Exp Ther Med

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Expression of autophagy-related proteins, microtubule-associated protein light chain 3 (LC3) and Beclin1, and matrix metalloproteinase-2 (MMP-2) was investigated in serum and peritoneal fluid of patients with endometriosis (EM). The messenger ribonucleic acid (mRNA) expression levels of MMP-2, LC3 and Beclin1 in endometrial tissues of EM patients and correlation of these genes with EM and their significance were evaluated. The serum, peritoneal fluid and endometrial tissues of 84 patients treated in The First Affiliated Hospital of Qiqihar Medical University (Qiqihar, China) from March 2016 to March 2017 were collected. The serum, peritoneal fluid and endometrial tissues of 42 EM patients were used as the experimental group, while those of 42 non-EM patients were used as the control group. The levels of LC3, Beclin1 and MMP-2 in serum and peritoneal fluid of EM patients and non-EM patients were quantitatively detected via enzyme-linked immunosorbent assay (ELISA), followed by comparative analysis based on data in both groups. In addition, mRNA expression of LC3, Beclin1 and MMP-2 in the endometrium in both groups were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and differences in expression of these genes between the groups were analyzed and evaluated. Correlation of LC3, Beclin1 and MMP-2 with EM was explored. Results of ELISA showed that levels of LC3 and Beclin1 in the EM group were significantly lower than those in the control group, while levels of MMP-2 in serum and peritoneal fluid of the EM group were significantly higher than those in the control group (P<0.05). Results of RT-qPCR revealed that mRNA expression of LC3 and Beclin1 in the endometrium of patients in the EM group were obviously decreased compared with those in the control group, while the expression of MMP-2 was high, and differences in expression were statistically significant (P<0.05). The expression of MMP-2 is high, and expression of LC3 and Beclin1 is low in serum, peritoneal fluid and endometrium of EM patients, and investigating the expression of MMP-2, LC3 and Beclin1 in EM is helpful to further clarify the pathogenesis of EM, and guide the clinical diagnosis and treatment.

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“…In a rat model of alcoholic liver disease, RA treatment downregulated MMP-2 and MMP-9 expression, as well as TIMPs expression ( 137 ), but could enhance MMP-3 and MMP-13 expression in HSC rat cell line ( 144 ). In addition RA can promote the upregulation of MMPs in dendritic cells ( 156 ) or mesenchymal stem cells ( 157 ) causing their enhanced migration to the site of injury.…”

Section: Il-17a Il-22 and Ra In Liver Fibrosismentioning

confidence: 99%

Retinoic Acid: A New Old Friend of IL-17A in the Immune Pathogeny of Liver Fibrosis

2021

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Despite all the medical advances mortality due to cirrhosis and hepatocellular carcinoma, the end stages of fibrosis, continuously increases. Recent data suggest that liver fibrosis is guided by type 3 inflammation with IL-17A at the top of the line. The storage of vitamin A and its active metabolites, as well as genetics, can influence the development and progression of liver fibrosis and inflammation. Retinoic acid (active metabolite of vitamin A) is able to regulate the differentiation of IL-17A+/IL-22–producing cells as well as the expression of profibrotic markers. IL-17A and its pro-fibrotic role in the liver is the most studied, while the interaction and communication between IL-17A, IL-22, and vitamin A–active metabolites has not been investigated. We aim to update what is known about IL-17A, IL-22, and retinoic acid in the pathobiology of liver diseases.

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All-trans retinoic acid enhances in vitro mesenchymal stem cells migration by targeting matrix metalloproteinases 2 and 9

Abstract: ATRA increases the in vitro migration capacity of the MSCs through stimulating the expression and activity of MMP-2/-9 and inhibiting caspase three enzyme activity.

Cited by 16 publications

References 14 publications

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

Retinol/inflammation affect stemness and differentiation potential of gingival stem/progenitor cells via Wnt/β‐catenin

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

Retinoic Acid: A New Old Friend of IL-17A in the Immune Pathogeny of Liver Fibrosis

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