DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2025
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IF 2.4
Hao Wang,Junfu Guo,Xuanyi Chen,Siqi Liu,Wenna Li,Lu Yang,Jianmiao Wang,Yinglun Han
The regulation of inflammatory balance is central to immune homeostasis, with disruptions contributing to autoimmune diseases. As representatives of early vertebrates, lampreys offer a valuable model for investigating the evolutionary foundations of immune regulation. This study examines the dual role of L-TGF-β2 in modulating inflammation in lampreys, providing insights into the evolutionary origins of immune homeostasis mechanisms. Using lipopolysaccharide (LPS)-induced inflammation models, recombinant L-TGF-β2 was found to enhance leukocyte chemotaxis in quiescent states while inhibiting excessive migration during activation. Quantitative PCR revealed that L-TGF-β2 stimulates pro-inflammatory cytokine expression during early inflammatory phases and attenuates it during resolution. Tissue-specific expression patterns of TGF-β receptors indicated their potential role in mediating the distinct regulatory effects of L-TGF-β2 across diverse immune environments. These findings align with the biphasic functions of TGF-β observed in higher vertebrates, underscoring the evolutionary conservation of this signaling pathway. This research enhances understanding the functional versatility of TGF-β signaling and its pivotal role in vertebrate immune evolution, providing insights into ancient mechanisms of immune homeostasis and their modern implications for inflammatory disease research.
研究领域:
免疫学
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进化生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
Liu Siqi,Guo Junfu,Cheng Xianda,Li Wenna,Lyu Shuangyu,Chen Xuanyi,Li Qingwei,Wang Hao
The transforming growth factor-βs (TGF-βs) are multifunctional cytokines capable of regulating a wide range of cellular behaviors and play a key role in maintaining the homeostasis of the immune system. The TGF-β subfamily, which is only present in deuterostomes, expands from a single gene in invertebrates to multiple members in jawed vertebrates. However, the evolutionary processes of the TGF-β subfamily in vertebrates still lack sufficient elucidation. In this study, the TGF-β homologs are identified at the genome-wide level in the reissner lamprey (Lethenteron reissneri), the sea lamprey (Petromyzon marinus), and the Japanese lamprey (Lampetra japonica), which are the extant representatives of jawless vertebrates with a history of more than 350 million years. The molecular evolutionary analyses reveal that the lamprey TGF-β subfamily contains two members representing ancestors of TGF-β2 and 3 in vertebrates, respectively, but TGF-β1 is absent. The transcriptional expression patterns show that the lamprey TGF-β2 may play a central regulatory role in the innate immune response of the lamprey since it exhibits a more rapid and significant upregulation of expression than TGF-β3 during lipopolysaccharide stimuli. The incorporation of BrdU assay reveals that the lamprey TGF-β2 recombinant protein exerts the bipolar regulation on the proliferation of the supraneural myeloid body cells (SMB cells) in the quiescent and LPS-activated state, while plays an inhibitory role in the proliferation of quiescent and activated leukocytes in lampreys. Furthermore, caspase-3/7 activity analysis indicates that the lamprey TGF-β2 protects SMB cells from apoptosis after serum deprivation, in contrast to promoting apoptosis of leukocytes. Our composite results offer valuable clues to the origin and evolution of the TGF-β subfamily and imply that TGF-βs are among the most ancestral immune regulators in vertebrates.
研究领域:
进化生物学
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免疫学
·
分子生物学
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基因组学
✓ 已验证
DOI
PubMed
高影响因子
Small
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2023
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IF 13.3
Sheng Meng,Qian Wei,Shengqiu Chen,Xi Liu,Shengnan Cui,Qilin Huang,Ziqiang Chu,Kui Ma,Wenhua Zhang,Wenzhi Hu,Shiyi Li,Zihao Wang,Lige Tian,Zhiliang Zhao,Haihong Li,Xiaobing Fu,Cuiping Zhang
Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-β2 to suppress the TGF-β2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3p OE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3p OE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3p OE -Exos are further fabricated in vivo. MiR-141 OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-β2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.
研究领域:
生物技术
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药学
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再生医学
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
2023
·
IF 2.9
Junfu Guo,Shuangyu Lyu,Yanchen Qi,Xuanyi Chen,Lu Yang,Chunhui Zhao,Hao Wang
Ferritin, one of the key regulators of iron homeostasis, is widely present throughout almost all species. The vertebrate ferritin family, which originates from a single gene in the ancestral invertebrates, contains the widest variety of ferritin subtypes among all animal species. However, the evolutionary history of the vertebrate ferritin family remains to be further clarified. In this study, genome-wide identification of the ferritin homologs is performed in lampreys, which are the extant representatives of jawless vertebrates that diverged from the future jawed vertebrates more than 500 million years ago. Molecular evolutionary analyses show that four members of the lamprey ferritin family, L-FT1–4, are derived from a common ancestor with jawed vertebrate ferritins prior to the divergence of the jawed vertebrate ferritin subtypes. The lamprey ferritin family shares evolutionarily conserved characteristics of the ferritin H subunit with higher vertebrates, but certain members such as L-FT1 additionally accumulate some features of the M or L subunits. Expression profiling reveals that lamprey ferritins are highly expressed in the liver. The transcription of L-FT1 is significantly induced in the liver and heart during lipopolysaccharide stimulation, indicating that L-FTs may play a role in the innate immune response to bacterial infection in lampreys. Furthermore, the transcriptional expression of L-FT1 in quiescent and LPS-activated leukocytes is up- and down-regulated by the lamprey TGF-β2, an essential regulator of the inflammatory response, respectively. Our results provide new insights into the origin and evolution of the vertebrate ferritin family and reveal that lamprey ferritins may be involved in immune regulation as target genes of the TGF-β signaling pathway.
研究领域:
分子进化
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免疫学
·
基因组学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
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