MicroRNAs can effectively induce formation of insulin-producing cells from mesenchymal stem cells

Bai, Chunyu; Gao, Yuhua; Li, Xiangchen; Wang, Kunfu; Xiong, Hui; Shan, Zhiqiang; Zhang, Ping; Wang, Wenjie; Guan, Weijun; Ma, Yue

doi:10.1002/term.2259

Cited by 32 publications

(32 citation statements)

References 56 publications

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“…In our previous report (Bai et al, 2017a), miR-375 and miR-26a combined with niacinamide were shown to promote beta cell differentiation from MSCs. We, therefore, determined the protein levels of the targets of miR-375 and miR-26a, namely Sox6, Bhlhe22, and Mtpn, and found these proteins to be markedly down-regulated after cocktail factor treatment, while the opposite trend was observed when the expression of miR-375 and miR-26a was inhibited in induced MSCs (Figure 3B).…”

Section: Pancreatic Mirnas Also Exhibited Increased Expression From Smentioning

confidence: 86%

“…On day 7, 10 mM ATRA was added. On day 9, the medium was replaced with fresh medium supplemented with 1% B27, 10 ng/mL bFGF, 10 mM nicotinamide, and 1% ITS to encourage further differentiation (Bai et al, 2017a). On day 16, the cocktail factors were used to induce MSCs to achieve terminal beta cell differentiation, and the culture media was then replaced with beta cell media (DMEM medium containing 25 mM glucose, 70 µM β-mercaptoethanol, and 4 mM L-glutamine, and supplemented with 15% FBS).…”

Section: Umbilical Cord Msc Culture and Differentiation Into Beta Cellsmentioning

confidence: 99%

“…Transplantation in vivo was executed as previously described (Shi et al, 2005;Bai et al, 2017a). All animal procedures were approved by the Institutional Animal Care and Use Committee of the Jining Medical University.…”

Section: Transplantation In Vivomentioning

confidence: 99%

“…The role of miRNAs in the regulation of beta cell differentiation has been demonstrated by the generation of a mouse model with beta cell-specific ablation of Dicer1 (Plaisance et al, 2014;Bai et al, 2016), and disruption of Dicer1 in rats with the use of a insulin promoter 2 (RIP)-Cre transgene results in changed islet morphology, reduced pancreatic beta cell numbers, and dysregulated glucose-induced insulin secretion (GSIS) (Kalis et al, 2011). Many miRNAs have been shown to be important regulators in the differentiation and function of pancreatic beta cells, including let-7 (Krek et al, 2005;Lovis et al, 2008), miR-223, miR-21 (Du Rieu et al, 2010Bai et al, 2016), miR-200, miR-30d, miR-124a (Tang et al, 2009), miR-26 (Bai et al, 2017a), miR-24, miR-148 (Melkman-Zehavi et al, 2011, miR-204 (Roldo et al, 2006), and miR-375 (Poy et al, 2004), as well as miR-146a, miR-15a, miR-29a, miR-9, miR-16, and miR-34 (Rosero et al, 2010;Bai et al, 2017b). However, as yet, there have been no reports regarding the role of induction factors in promoting the transcription of pancreatic miRNAs during beta cell differentiation from stem cells, and the molecular mechanisms underlying this process remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Activins are dimeric proteins composed of either two βA subunits (activin A), two βB subunits (activin B) or a βA and βB subunit (activin AB). Activin A is extensively involved in the production of beta cells from stem cells (Shi et al, 2005;Pagliuca et al, 2014;Bai et al, 2017a) but the functions of the TGF-β pathway in beta cell differentiation and pancreatic miRNA expression have not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

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Role of TGF-β/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation

Gao¹,

Zhang²,

Dai³

et al. 2019

Front. Cell Dev. Biol.

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Autoimmune destruction of pancreatic beta cells causes absolute insulin deficiency and results in type 1 diabetes mellitus (T1DM). The substitution of healthy pancreatic beta cells for damaged cells would be the ideal treatment for T1DM; thus, the generation of pancreatic beta cells from adult stem cells represents an attractive avenue for research. In this study, a cocktail of factors was used to induce the differentiation of pancreatic beta cells from mesenchymal stem cells (MSCs). The differentiation program was divided into five stages, and the roles of the cocktail factors used during each stage were systematically elucidated. Activin A was found to phosphorylate Smad2 and Smad3 in stage III, thereby activating the TGF-β/Smad pathway. Meanwhile, the endocrine-specific transcription factor, Ngn3, and the pancreas-specific miRNAs, miR-375 and miR-26a, were dramatically elevated in stage III. We next demonstrated that Smad4, an important transcription factor in the TGF-β/Smad pathway, could bind to the promoter sequences of target genes and enhance their transcription to initiate the differentiation of beta cells. Use of SB-431542, an inhibitor of the TGF-β/Smad pathway, demonstrated in vivo and in vitro that this pathway plays a critical role in the production of pancreatic beta cells and in modulating insulin secretion. Thus, the TGF-β/Smad pathway is involved in the production of beta cells from adult stem cells by enhancing the transcription of Ngn3, miR-375, and miR-26a. These findings further underline the significant promise of cell transplant therapies for type 1 diabetes mellitus.

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Section: Pancreatic Mirnas Also Exhibited Increased Expression From Smentioning

confidence: 86%

Section: Umbilical Cord Msc Culture and Differentiation Into Beta Cellsmentioning

confidence: 99%

Section: Transplantation In Vivomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of TGF-β/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation

Gao¹,

Zhang²,

Dai³

et al. 2019

Front. Cell Dev. Biol.

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Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function

Zhao

Rong

Pan

et al. 2018

J of Cellular Biochemistry

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Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes.

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MicroRNAs’ role in the environment-related non-communicable diseases and link to multidrug resistance, regulation, or alteration

Mahmoud

Sanad

Hamdy

2021

Environ Sci Pollut Res

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Discovery of microRNAs (miRNAs) twenty years ago, has advocated a new era of "Molecular Genetics". About 2000 miRNAs are present, that regulate one third of the genome. MiRNAs dysregulated expression may contribute to several diseases including tumor growth. Their presence in body fluids, reflecting levels alteration in various cancers, merit circulating miRNAs as the "next generation biomarkers" for early stages tumor diagnosis and/or prognosis. Herein, we performed a comprehensive literature search focusing on the origin, biosynthesis and role of miRNAs and summarized the foremost studies centering on miRs value as non-invasive biomarkers in different non-communicable diseases, including various cancer types. Moreover, during chemotherapy many miRNAs were linked to multidrug resistance, via modulating numerous biological processes and/or pathways that will be highlighted as well.

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MicroRNAs can effectively induce formation of insulin-producing cells from mesenchymal stem cells

Cited by 32 publications

References 56 publications

Role of TGF-β/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation

Role of TGF-β/Smad Pathway in the Transcription of Pancreas-Specific Genes During Beta Cell Differentiation

Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function

MicroRNAs’ role in the environment-related non-communicable diseases and link to multidrug resistance, regulation, or alteration

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