Quantitative analysis of protein and gene expression in salivary glands of Sjogren's-like disease NOD mice treated by bone marrow soup.

Quantitative analysis of protein and gene expression in salivary glands of Sjogren's-like disease NOD mice treated by bone marrow soup.
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DOI:
10.1371/journal.pone.0087158
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Hu S
Hu S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Misuno K;Tran SD;Khalili S;Huang J;Liu Y;Hu S

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骨髓细胞提取物(称为BM汤)在我们以前的研究中已被证明可以修复辐射唾液腺(SG)并恢复唾液分泌。在本研究中,我们的目的是研究非肥胖糖尿病(NOD)小鼠中受损的SG的功能是否可以通过BM汤治疗以及与治疗相关的分子改变来恢复。将整个BM细胞裂解,并将可溶性细胞内内容物(“BM汤”)静脉内注射到NOD小鼠中。使用串联质量标记与2-D液相色谱-质谱法来定量未处理和BM汤处理的小鼠之间的下颌下腺(SMG)中的蛋白质。使用定量PCR来鉴定经处理的小鼠中具有改变的表达的基因。恢复唾液流速到正常水平,并显着降低NOD小鼠SMG的焦点得分。通过蛋白质组学方法定量了SMG细胞中超过1800种蛋白质。发现参与炎症和细胞凋亡的许多SMG蛋白在BM汤处理的小鼠中下调,而参与唾液腺生物学和发育/再生的SMG蛋白在BM汤处理的小鼠中上调。qPCR分析还揭示了经治疗的NOD小鼠的SMG中生长因子和细胞因子的表达变化。BM汤治疗能有效恢复NOD小鼠受损的SG功能。通过基因/蛋白表达分析,我们发现BM汤治疗可能通过抑制NOD小鼠SG细胞的凋亡、粘着斑和炎症,而促进SG细胞的发育、再生和分化来实现。这些发现为BM汤治疗NOD小鼠受损SG的功能恢复的潜在机制提供了重要的见解。需要进一步的研究来进一步确认确定的靶基因及其相关的信号通路,这些基因和信号通路是BM Soup治疗的原因。
Bone marrow cell extract (termed as BM Soup) has been demonstrated to repair irradiated salivary glands (SGs) and restore saliva secretion in our previous study. In the present study, we aim to investigate if the function of damaged SGs in non-obese diabetic (NOD) mice can be restored by BM Soup treatment and the molecular alterations associated with the treatment. Whole BM cells were lysed and soluble intracellular contents (“BM Soup”) were injected I.V. into NOD mice. Tandem mass tagging with 2-D liquid chromatography-mass spectrometry was used to quantify proteins in the submandibular glands (SMGs) between untreated and BM Soup-treated mice. Quantitative PCR was used to identify genes with altered expression in the treated mice. restored salivary flow rates to normal levels and significantly reduced the focus scores of SMGs in NOD mice. More than 1800 proteins in SMG cells were quantified by the proteomic approach. Many SMG proteins involved in inflammation and apoptosis were found to be down-regulated whereas those involved in salivary gland biology and development/regeneration were up-regulated in the BM Soup-treated mice. qPCR analysis also revealed expression changes of growth factors and cytokines in the SMGs of the treated NOD mice. BM Soup treatment is effective to restore the function of damaged SGs in NOD mice. Through gene/protein expression analysis, we have found that BM Soup treatment might effectuate via inhibiting apoptosis, focal adhesion and inflammation whereas promoting development, regeneration and differentiation of the SG cells in NOD mice. These findings provide important insights on the potential mechanisms underlying the BM Soup treatment for functional restoration of damaged SGs in NOD mice. Additional studies are needed to further confirm the identified target genes and their related signaling pathways that are responsible for the BM Soup treatment.
DOI: 10.1002/art.24150
发表时间: 2009-01
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DOI: 10.1515/bc.2001.013
发表时间: 2001-01-01
影响因子: 3.7
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