Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells

Purvis, Nima; Kumari, Sweta; Chandrasekera, Dhananjie; Papannarao, Jayanthi Bellae; Gandhi, Sophie; Hout, Isabelle van; Coffey, Sean; Bunton, Richard; Sugunesegran, Ramanen; Parry, Dominic; Davis, Philip J.; Williams, Michael J.A.; Bahn, Andrew; Katare, Rajesh

doi:10.1007/s00125-021-05405-7

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…MiR-30b-5p overexpression could reduce intracellular lipid deposition and regulate intracellular lipid metabolism by targeting PPAR-α and GLUT1, thus triggering mitochondrial oxidative phosphorylation, fatty acidbeta-oxidation and synthesis, glucose uptake, and gluconeogenesis. Also, the mucin-type O-glycan biosynthesis pathway (pathway 2) appears solely associated with hsa-miR-30b-5p, which controls a group of isoenzymes that initiate several glycosylation reactions [48][49][50]. Aberrant expression of glycan has been reported in most hematological malignancies, such as AML, myeloproliferative neoplasms, and multiple myeloma, as well in bone-marrow-associated breast cancer cell dissemination [51][52][53].…”

Section: Resultsmentioning

confidence: 99%

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

Cappelli,

Ravera,

Bertola

et al. 2024

Genes

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Some years ago, we reported the generation of a Fanconi anemia (FA) microRNA signature. This study aims to develop an analytical strategy to select a smaller and more reliable set of molecules that could be tested for potential benefits for the FA phenotype, elucidate its biochemical and molecular mechanisms, address experimental activity, and evaluate its possible impact on FA therapy. In silico analyses of the data obtained in the original study were thoroughly processed and anenrichment analysis was employed to identify the classes of genes that are over-represented in the FA-miRNA population under study. Primary bone marrow mononuclear cells (MNCs) from sixFA patients and sixhealthy donors as control samples were employed in the study. RNAs containing the small RNA fractions were reverse-transcribed and real-time PCR was performed in triplicate using the specific primers. Experiments were performed in triplicate.The in-silico analysis reported six miRNAs as likely contributors to the complex pathological spectrum of FA. Among these, three miRNAs were validated by real-time PCR. Primary bone marrow mononuclear cells (MNCs) reported a significant reduction in the expression level of miRNA-1246 and miRNA-206 in the FA samples in comparison to controls.This study highlights several biochemical pathways as culprits in the phenotypic manifestations and the pathophysiological mechanisms acting in FA. A relatively low number of miRNAs appear involved in all these different phenotypes, demonstrating the extreme plasticity of the gene expression modulation. This study further highlights miR-206 as a pivotal player in regulatory functions and signaling in the bone marrow mesenchymal stem cell (BMSC) process in FA. Due to this evidence, the activity of miR-206 in FA deserves specific experimental scrutiny. The results, here presented, might be relevant in the management of FA.

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Section: Resultsmentioning

confidence: 99%

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

Cappelli,

Ravera,

Bertola

et al. 2024

Genes

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“…On the other hand, miR-30c was induced during adipogenesis but was downregulated in obese adipocytes [113]. Furthermore, diabetes mellitus significantly downregulated miR-30c-5p associated with stem cell survival, proliferation, and differentiation in cardiac progenitor cells [114]. The last of the analysed miRNAs was miR-21,s which was significantly downregulated in insulinresistant adipocytes [115].…”

Section: Discussionmentioning

confidence: 98%

A Comparative Study of Equine Hoof Progenitor Cells and Adipose-Derived Stem Cells in Hyperinsulinemia

Pielok,

Króliczewski,

Kępska

et al. 2023

Preprint

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Recently, we isolated and characterized a new pool of mesenchymal stem cells- HPC (Hoof Progenitor Cells), which reside in the coronary corium of equine hooves. We hypothesize, that due to their location, HPC may be involved in the pathogenesis of laminitis, and could possibly be utilized in its treatment. The aim of this study was to compare the newly described HPC to a well-established cell pool-ASC (Adipose Stem Cells). The two cell populations were maintained either in standard culture conditions or under a hyperinsulinemic milieu as hyperinsulinemia is often observed alongside laminitis. Cell cycle dynamics, mitochondrial membrane potential and oxidative stress were analyzed with microcapillary cytometry. Furthermore, the expression of key markers of mitochondrial metabolism, oxidative stress, apoptosis, immunomodulation and insulin signalling were analyzed with the RT-qPCR method. Additionally, a selected panel of miRNA was analyzed with the RT-qPCR method. In standard culture conditions, ASC exhibit higher proliferation than HPC while in hyperinsulinemia a shift towards S phase was observed in both populations. As for the mitochondrial membrane potential, in standard culture conditions, HPC was characterized by a higher percent of live cells. Hyperinsulinemia did not strongly affect the mitochondrial membrane potential of the analyzed populations. Our findings indicate that HPC are characterized by higher activity in terms of mitochondrial dynamics, mitophagy, and mitochondrial biogenesis under standard culture conditions. Yet in both populations, a diminished mitochondrial dynamic and metabolism was observed in hyperinsulinemia. The analysis of oxidative stress revealed, that HPC might possess somewhat higher resistance towards oxidative stress than ASC. Minimal change was observed in the expression of key markers of apoptosis in ASC and HPC under hyperinsulinemia. The analysis of key immunomodulatory markers indicated that HPC may help the cytokine storm for a more effective phenotype change to an immunosuppressing pool of cells with better migratory and healing abilities under hyperinsulinemia than ASC. As for insulin signalling, the obtained data suggests that HPC might be more resistant to hyperinsulinemia and may have greater therapeutic potential in reducing laminitis. Obtained results demonstrated that HPC possesses better potential to modulate the PTEN-AKT pathway by miR-21 and reverse high glucose and high insulin-induced insulin resistance. Taken together, the obtained results indicate that HPC may be a very promising cell pool with therapeutic potential in laminitis treatment, and could be more effective than ASC.

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“…The results showed that compared to model group, ZSP induced PI3K/AKT signaling in both mRNA and protein levels. However, it is worth noting that the mRNA expression of PI3K and AKT are inconsistent with the protein expression in the normal group, which may be the result of potential different post-transcriptional regulations between the wt/wt and db/db mice [ 27 ]. Another explain for this phenomenon is that the insulin level in db/db mice is relatively high, and constant stimulation of insulin may also contribute to the elevated PI3K and AKT expression.…”

Section: Discussionmentioning

confidence: 99%

Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver

Sun

Guo

et al. 2022

Chin Med

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Background The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP’s hypoglycemic effects using db/db mice. Methods Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques. Results ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group. Conclusion ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver.

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Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells

Cited by 6 publications

References 49 publications

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

Advanced Analysis and Validation of a microRNA Signature for Fanconi Anemia

A Comparative Study of Equine Hoof Progenitor Cells and Adipose-Derived Stem Cells in Hyperinsulinemia

Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver

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