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1.
Genes (Basel) ; 10(9)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509970

RESUMO

The multiple organellar RNA editing factors (MORF) gene family plays a key role in organelle RNA editing in flowering plants. MORF genes expressions are also affected by abiotic stress. Although seven OsMORF genes have been identified in rice, few reports have been published on their expression patterns in different tissues and under abiotic stress, and OsMORF-OsMORF interactions. In this study, we analyzed the gene structure of OsMORF family genes. The MORF family members were divided into six subgroups in different plants based on phylogenetic analysis. Seven OsMORF genes were highly expressed in leaves. Six and seven OsMORF genes expressions were affected by cold and salt stresses, respectively. OsMORF-OsMORF interaction analysis indicated that OsMORF1, OsMORF8a, and OsMORF8b could each interact with themselves to form homomers. Moreover, five OsMORF proteins were shown to be able to interact with each other, such as OsMORF8a and OsMORF8b interacting with OsMORF1 and OsMORF2b, respectively, to form heteromers. These results provide information for further study of OsMORF gene function.

2.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500108

RESUMO

The chloroplast RNA splicing and ribosome maturation (CRM) domain proteins are involved in the splicing of chloroplast gene introns. Numerous CRM domain proteins have been reported to play key roles in chloroplast development in several plant species. However, the functions of CRM domain proteins in chloroplast development in rice remain poorly understood. In the study, we generated oscaf1 albino mutants, which eventually died at the seedling stage, through the editing of OsCAF1 with two CRM domains using CRISPR/Cas9 technology. The mesophyll cells in oscaf1 mutant had decreased chloroplast numbers and damaged chloroplast structures. OsCAF1 was located in the chloroplast, and transcripts revealed high levels in green tissues. In addition, the OsCAF1 promoted the splicing of group IIA and group IIB introns, unlike orthologous proteins of AtCAF1 and ZmCAF1, which only affected the splicing of subgroup IIB introns. We also observed that the C-terminal of OsCAF1 interacts with OsCRS2, and OsCAF1-OsCRS2 complex may participate in the splicing of group IIA and group IIB introns in rice chloroplasts. OsCAF1 regulates chloroplast development by influencing the splicing of group II introns.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1259-1264, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418390

RESUMO

OBJECTIVE: To explore the role of bone marrow microenvironment(niche) in the development of acute myeloid leukemia (AML) and the effect of AML patients-derived MSC on the proliferation, cell cycle and immuno-phenotypes of HL-60 cells. METHODS: The MSC derived from bone marrow of patients with newly diagnosed AML were isolated and co-cultured with HL-60 cells. The effect of MSC on proliferation of HL-60 cells was detected by using 3H-TdR incorporation method, the cell cycle and immunophenotypes of HL-60 cells were detected by flow cytometry. RESULTS: The results of 3H-TdR incorporation assay showed that both AML-MSCs and normal MSCs remarkably suppressed the HL-60 cell proliferation in a time- and dose-dependent manner. The results of cell cycle analysis demonstrated that AML MSCs and normal MSCs induced arrest of the HL-60 cells in G0/G1 phase. The results of immunophenotyping revealed that MSCs suppressed the expression of CD11a and CD154 on the surface of HL-60 cells. Moreover, AML MSCs exhibited increased inhibitory effects than that of normal MSCs. However, no remarkable effect of MSCs on CD54 expressions of HL-60 cells was observed in the current study. CONCLUSION: AML-MSCs possess effects on HL-60 cell proliferation, cell cycle and immunophenotypes similiar to normal MSCs, but exhibited increased suppressive capacity on the expression of CD11a and CD154.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Células da Medula Óssea , Ciclo Celular , Proliferação de Células , Células HL-60 , Humanos , Imunofenotipagem , Microambiente Tumoral
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1277-1286, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418393

RESUMO

OBJECTIVE: To study the influence of acute myeloid leukemia (AML) microenvironment on mesenchymal stem cells (MSCs). METHODS: MSCs were isolated from the bone marrow of newly diagnosed AML patients (AML-MSCs) and were cultured. The morphology of MSC was observed by inverted microscopy, the immunophenotypes of MSC were detected by flow cytometry, the proliferation ability of MSC was detected by using MTT method, the multi-differentation ability of MSC was assayed by osteogenic, lipogenic and chrondrogenic induction. The morphologic features, immunophenotypic characteristics, cell proliferation, and multipotential differentiation capability were compared between the MSC derived from normal healthy donors and AML patients. RESULTS: AML-MSCs presented the morphological features similar to the normal MSCs. In addition, AML-MSCs highly expressed CD29, CD44, CD73, CD105 and HLA-ABC. Meanwhile, they were homogenously negative for CD14,CD31, CD34, CD45, CD80, CD86 and HLA-DR. Further-more, AML-MSCs showed cell proliferation ability similar to normal MSCs. Notably, AML-MSCs exerted increased osteogenic-differentiation capacity as compared with normal MSCs. CONCLUSION: AML-MSCs possess typical MSC phenotypes but displayed enhanced osteogenic-differentiation capacity.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Humanos , Osteogênese , Microambiente Tumoral
5.
Plant Signal Behav ; : 1-4, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397633

RESUMO

High light and high temperature (HLHT) stress induces the production of damaging reactive oxygen species (ROS) in many plants. Recently, we described a HLHT-sensitive rice (Oryza sativa) mutant, local lesions (ls1), that exhibits local lesions under HLHT, due to DNA damage and excess ROS accumulation. Here, we determined that an HLHT treatment induced the local lesion phenotype in ls1 within 6 h. Corroborating this result, we found that transient HLHT treatment influenced the expression of many genes in the ls1 mutant, while affecting the growth and development of young leaves.

6.
Plant J ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357245

RESUMO

The palea and lemma (hull) are grass-specific organs, and determine grain size and quality. In the study, AH2 encodes a MYB domain protein, and functions in the development of hull and grain. Mutation of AH2 produces smaller grains and alters grain quality including decreased amylose content and gel consistency, and increased protein content. Meantime, part of the hull lost the outer silicified cells, and induces a transformation of the outer rough epidermis to inner smooth epidermis cells, and the body of the palea was reduced in the ah2 mutant. We confirmed the function of AH2 by complementation, CRISPR-Cas9, and cytological and molecular tests. Additionally, AH2, as a repressor, repress transcription of the downstream genes. Our results revealed that AH2 plays an important role in the determination of hull epidermis development, palea identity, and grain size.

7.
Mol Ecol Resour ; 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325912

RESUMO

The red-spotted grouper Epinephelus akaara (E. akaara) is one of the most economically important marine fish in China, Japan and South-East Asia and is a threatened species. The species is also considered a good model for studies of sex inversion, development, genetic diversity and immunity. Despite its importance, molecular resources for E. akaara remain limited and no reference genome has been published to date. In this study, we constructed a chromosome-level reference genome of E. akaara by taking advantage of long-read single-molecule sequencing and de novo assembly by Oxford Nanopore Technology (ONT) and Hi-C. A red-spotted grouper genome of 1.135 Gb was assembled from a total of 106.29 Gb polished Nanopore sequence (GridION, ONT), equivalent to 96-fold genome coverage. The assembled genome represents 96.8% completeness (BUSCO) with a contig N50 length of 5.25 Mb and a longest contig of 25.75 Mb. The contigs were clustered and ordered onto 24 pseudochromosomes covering approximately 95.55% of the genome assembly with Hi-C data, with a scaffold N50 length of 46.03 Mb. The genome contained 43.02% repeat sequences and 5,480 noncoding RNAs. Furthermore, combined with several RNA-seq data sets, 23,808 (99.5%) genes were functionally annotated from a total of 23,923 predicted protein-coding sequences. The high-quality chromosome-level reference genome of E. akaara was assembled for the first time and will be a valuable resource for molecular breeding and functional genomics studies of red-spotted grouper in the future.

8.
Bioorg Med Chem ; 27(17): 3846-3852, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31324565

RESUMO

The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin ABBA and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6 µM), it was very exciting that dryocrassin ABBA and its analogues (b5 and e2) showed better NAs inhibitory activity against Anhui H7N9 with IC50 values of 3.6 µM, 2.5 µM and 1.6 µM. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin ABBA and its analogues especially AB, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.

9.
Postgrad Med J ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324728

RESUMO

BACKGROUND: Congenital heart disease (CHD) is among the leading causes of infant death worldwide. Although shortage of folate has been found potentially to contribute to CHD in the embryo, the aetiology of CHD was not completely understood. Inflammation and altered immune processes are involved in all forms of cardiac malformation, including CHD. Tumour necrosis factor-α (TNF-α), was involved in the pathogenesis of multiple kinds of heart diseases. However, no studies have systematically evaluated the associations of genetic variants of TNF-α with susceptibility of CHD. METHODS: A case-control study was conducted to evaluate the associations between tagSNPs of TNF-α and CHD susceptibility. Serum level of TNF-α was assessed using ELISA. The dual luciferase reporter assay was used to evaluate the functional significance of variant rs1800629 on TNF-α transcriptional activity. RESULTS: We found rs1800629 was significantly correlated with increased CHD susceptibility (OR: 1.72, 95% CI 1.26 to 2.36, p=0.001). Serum levels of TNF-α were significantly higher in CHD group (9.09±1.90 pg/mL) than that in control group (6.12±1.56 pg/mL, p<0.001). The AA genotype and AG genotype of rs1800629 was associated with higher serum TNF-α level, compared with GG genotype. The dual luciferase reporter assay showed that promoter activity was significantly increased by 57% and 76% for plasmids containing the minor A allele compared with the major G allele in H9c2 and HEK 293T, respectively. CONCLUSION: These results indicate that higher level of serum TNF-α increases risk of CHD, while TNF-α rs1800629 A allele might contribute to higher risk for CHD due to the increase in TNF-α expression.

10.
Ecotoxicol Environ Saf ; 180: 780-788, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31154203

RESUMO

Cadmium (Cd) is one of the most toxic heavy metals, and its accumulation in plants will seriously affect growth and yield. In this study, Cd-sensitive line D69 and Cd-tolerant line D28 were selected, which the Cd content of D28 was higher than D69 in both above and underground parts after Cd treatment. Using a combination of two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF MS/MS, the differential expression changes of phosphorylated proteins between D69 and D28 in leaves were classified and analyzed after Cd treatment. A total of 53 differentially expressed phosphoproteins were identified, which mainly involved in metabolism, signal transduction, gene expression regulation, material transport, and membrane fusion. The phosphorylated proteins of Cd-tolerant and Cd-sensitive lines were all analyzed, and found that some proteins associated with carbon metabolism, proteolytic enzymes, F-box containing transcription factors, RNA helicases, DNA replication/transcription/repair enzymes and ankyrins were detected in Cd-tolerant line D28, which might alleviate the abiotic stress caused by Cd treatment. These results will clarify the phosphorylated pathways in response and resistance to Cd stress in rice.


Assuntos
Cádmio/toxicidade , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Oryza/genética , Oryza/fisiologia , Fosforilação , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Poluentes do Solo/toxicidade
11.
J Asian Nat Prod Res ; : 1-8, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31154865

RESUMO

Three new monoterpenoid indole alkaloids, kopsiaofficines A-D (1-3), were isolated from the 95% EtOH extract of the aerial parts of Kopsia officinalis. Their structures were established on the basis of spectroscopic data. The isolated alkaloids were tested in vitro for cytotoxic activity against seven lung cancer cell lines. Consequently, alkaloids 1 and 3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 20 µM.

12.
Fitoterapia ; 136: 104178, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31121254

RESUMO

One hitherto unknown 24-nor-13,27-cycloursane-type triterpenoid, lucumic acid A (1), one new 24-nor-ursane triterpenoid, lucumic acid B (2), along with six known triterpenoids were isolated from the ethanol extract of the leaves of Lucuma nervosa. Their structures were established on the basis of spectroscopic data interpretation. Lucumic acid A (1) is the first example of a 24-nor-triterpenoid with a 13,27-cyclopropane ring.


Assuntos
Ácido Oleanólico/análogos & derivados , Folhas de Planta/química , Pouteria/química , Triterpenos/isolamento & purificação , China , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Estrutura Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Triterpenos/farmacologia
13.
Int J Radiat Oncol Biol Phys ; 105(1): 124-131, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075310

RESUMO

PURPOSE: To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI. METHODS AND MATERIALS: A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis. RESULTS: Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D2) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D2) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D2). CONCLUSIONS: In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D2) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.

14.
Plant Biotechnol J ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31141272

RESUMO

Heading date 1 (Hd1) is an important gene for the regulation of flowering in rice, but its variation in major cultivated rice varieties, and the effect of this variation on yield and quality, remains unknown. In this study, we selected 123 major rice varieties cultivated in China from 1936 to 2009 to analyse the relationship between the Hd1 alleles and yield-related traits. Among these varieties, 19 haplotypes were detected in Hd1, including two major haplotypes (H8 and H13) in the japonica group and three major haplotypes (H14, H15 and H16) in the indica group. Analysis of allele frequencies showed that the secondary branch number was the major aimed for Chinese indica breeding. In the five major haplotypes, SNP316 (C-T) was the only difference between the two major japonica haplotypes, and SNP495 (C-G) and SNP614 (G-A) are the major SNPs in the three indica haplotypes. Association analysis showed that H16 is the most preponderant allele in modern cultivated Chinese indica varieties. Backcrossing this allele into the japonica variety Chunjiang06 improved yield without decreasing grain quality. Therefore, our analysis offers a new strategy for utilizing these preponderant alleles to improve yield and quality of japonica varieties for cultivation in the southern areas of China.

15.
BMC Plant Biol ; 19(1): 170, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039733

RESUMO

BACKGROUND: Endo-ß-1,4-xylanase1 (EA), the key endoxylanase in plants, is involved in the degradation of arabinoxylan during grain germination. In barley (Hordeum vulgare L.), one gene (HvXYN-1) that encode a endo-beta-1,4-xylanase, has been cloned. However, the single nucleotide polymorphisms (SNPs) that affect the endoxylanase activity and total arabinoxylan (TAX) content have yet to be characterized. The investigation of genetic variation in HvXYN1 may facilitate a better understanding of the relationship between TAX content and EA activity in barley. RESULTS: In the current study, 56 polymorphisms were detected in HvXYN1 among 210 barley accessions collected from 34 countries, with 10 distinct haplotypes identified. The SNPs at positions 110, 305, 1045, 1417, 1504, 1597, 1880 bp in the genomic region of HvXYN1 were significantly associated with EA activity (P < 0.0001), and the sites 110, 305, and 1045 were highly significantly associated with TAX content. The amount of phenotypic variation in a given trait explained by each associated polymorphism ranged from 6.96 to 9.85%. Most notably, we found two variants at positions 1504 bp and 1880 bp in the second exon that significantly (P < 0.0001) affected EA activity; this result could be used in breeding programs to improve beer quality. In addition, African accessions had the highest EA activity and TAX content, and the richest germplasm resources were from Asia, indicating the high potential value of Asian barley. CONCLUSION: This study provided insight into understanding the relationship, EA activity, TAX content with the SNPs of HvXYN1 in barley. These SNPs can be applied as DNA markers in breeding programs to improve the quality of barley for beer brewing after further validation.


Assuntos
Endo-1,4-beta-Xilanases/metabolismo , Variação Genética , Hordeum/genética , Proteínas de Plantas/genética , Xilanos/metabolismo , Alelos , Endo-1,4-beta-Xilanases/genética , Haplótipos , Hordeum/enzimologia , Filogeografia , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único
16.
Nat Genet ; 51(5): 865-876, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043757

RESUMO

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaea and other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42-0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.


Assuntos
Arachis/genética , Arachis/embriologia , Arachis/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Resistência à Doença/genética , Domesticação , Secas , Ecótipo , Evolução Molecular , Genoma de Planta , Cariótipo , Óleo de Amendoim/metabolismo , Melhoramento Vegetal , Doenças das Plantas/prevenção & controle , Proteínas de Vegetais Comestíveis/metabolismo , Poliploidia , Sementes/anatomia & histologia , Sementes/genética
17.
J Asian Nat Prod Res ; : 1-8, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31046464

RESUMO

Three new isoquinoline alkaloids, including two aporphines (1 and 2) and one oxoaporphine (3), were isolated from the 90% EtOH extract of the whole plants of Thalictrum tenue Franch. The structures of the isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry, respectively. The isolated alkaloids were tested in vitro for cytotoxic activity against six esophageal carcinoma cell lines. Consequently, alkaloids 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 20 µM.

18.
Zhongguo Zhong Yao Za Zhi ; 44(4): 717-722, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30989884

RESUMO

Eight C_(19)-diterpenoid alkaloids( 1-8) were isolated from the ethyl acetate soluble fraction of 95% ethanol extract of the ground roots of Aconitum austroyunnanense through various column chromatographies on silica gel,ODS,Sephadex LH-20 and MCI gel.Their structures were elucidated as 14α-benzoyloxy-13ß,15α-dihydroxy-1α,6α,8ß,16ß,18-pentamethoxy-19-oxoaconitan( 1),N-deethylaconitine( 2),spicatine B( 3),leucanthumsine A( 4),acofamine B( 5),macrorhynine B( 6),aconitilearine( 7),and ambiguine( 8) based on their chemical and physicochemical properties and spectroscopic data. Compound 1 was a new compound and alkaloids 2-8 were isolated from this plant for the first time. Some isolated alkaloids were tested in vitro for cytotoxic potential by employing the MTT method. As a result,alkaloid 1 exhibited weak cytotoxic activity against three tested tumor cell lines( A-549,He La,and Hep G2) with IC_(50) values less than 20 µmol·L~(-1).


Assuntos
Aconitum , Alcaloides , Diterpenos , Estrutura Molecular , Raízes de Plantas
20.
JCI Insight ; 4(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30996131

RESUMO

The identification of new sources of ß cells is an important endeavor with therapeutic implications for diabetes. Insulin resistance, in physiological states such as pregnancy or in pathological states such as type 2 diabetes (T2D), is characterized by a compensatory increase in ß cell mass. To explore the existence of a dynamic ß cell reserve, we superimposed pregnancy on the liver-specific insulin receptor-KO (LIRKO) model of insulin resistance that already exhibits ß cell hyperplasia and used lineage tracing to track the source of new ß cells. Although both control and LIRKO mice displayed increased ß cell mass in response to the relative insulin resistance of pregnancy, the further increase in mass in the latter supported a dynamic source that could be traced to pancreatic ducts. Two observations support the translational significance of these findings. First, NOD/SCID-γ LIRKO mice that became pregnant following cotransplantation of human islets and human ducts under the kidney capsule showed enhanced ß cell proliferation and an increase in ductal cells positive for transcription factors expressed during ß cell development. Second, we identified duct cells positive for immature ß cell markers in pancreas sections from pregnant humans and in individuals with T2D. Taken together, during increased insulin demand, ductal cells contribute to the compensatory ß cell pool by differentiation/neogenesis.

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