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在体研究和 BDMC33 对斑马鱼肠道炎症相关关节炎中 TNBS 诱导的 BMP 基因表达的影响。

In Silico Study and Effects of BDMC33 on TNBS-Induced BMP Gene Expressions in Zebrafish Gut Inflammation-Associated Arthritis.

机构信息

Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.

Department of Cell and Molecular Biology, Faculty of Biotechnology and Bimolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.

出版信息

Molecules. 2022 Nov 28;27(23):8304. doi: 10.3390/molecules27238304.

DOI:10.3390/molecules27238304
PMID:36500396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9740523/
Abstract

The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut-joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected genes in the TNBS-induced larvae, where the highest gene suppression was in the gene (an eight-fold decrement), followed by (four-fold decrement), (four-fold decrement), and (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced genes in zebrafish larvae.

摘要

骨形态发生蛋白(BMP)家族是 TGF-β超家族的成员,在肠道炎症和关节炎疾病的发生中起着至关重要的作用。最近的研究报告称,它与肠道-关节轴有关;然而,遗传因素仍未得到充分探索。同时,BDMC33 是一种新合成的抗炎药物候选物。因此,在我们目前的研究中,我们分析了 BMP 家族的全基因组特征,以及 BMP 成员在炎症状态下与肠道相关关节炎的关系,以及 BDMC33 减轻这种炎症的能力。首先,我们使用几种计算机技术对斑马鱼基因组中的 BMP 家族进行了全基因组分析。然后,使用实时 qPCR 测定姜黄素类似物对 TNBS(0.78mg/mL)诱导的斑马鱼幼虫基因表达的影响。总共鉴定出 38 种 BMP 蛋白,它们聚类在五个主要分支中,包含 TGF-β和 TGF-β前肽结构域。此外,BDMC33 抑制了 TNBS 诱导的幼虫中四个选定基因的表达,其中抑制作用最强的是 基因(八倍降低),其次是 基因(四倍降低)、 基因(四倍降低)和 基因(三倍降低)。因此,本研究揭示了 BMP 在肠道相关关节炎中的作用,并证明了 BDMC33 作为一种潜在的抗炎药物,能够抑制 TNBS 诱导的斑马鱼幼虫中基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/ae0b115ac765/molecules-27-08304-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/22b38d2e7c1f/molecules-27-08304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/6d3df922e198/molecules-27-08304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/7250162abd5f/molecules-27-08304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/40fde2804b1f/molecules-27-08304-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/552a1c8a398c/molecules-27-08304-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/98d09bcac973/molecules-27-08304-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/38533fa4caaa/molecules-27-08304-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/ae0b115ac765/molecules-27-08304-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/22b38d2e7c1f/molecules-27-08304-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/6d3df922e198/molecules-27-08304-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/7250162abd5f/molecules-27-08304-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/40fde2804b1f/molecules-27-08304-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/552a1c8a398c/molecules-27-08304-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/98d09bcac973/molecules-27-08304-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/38533fa4caaa/molecules-27-08304-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b4/9740523/ae0b115ac765/molecules-27-08304-g008.jpg

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