PLoS Genetics
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2021
·Vol. 17
·期 7
·e1009649
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IF 5.917
Kun Wu,Yiming Tang,Qiaoqiao Zhang,Zhangpeng Zhuo,Xiao Sheng,Jingping Huang,Jie’er Ye,Xiaorong Li,Zhiming Liu,Haiyang Chen
The differentiation efficiency of adult stem cells undergoes a significant decline in aged animals, which is closely related to the decline in organ function and age-associated diseases. However, the underlying mechanisms that ultimately lead to this observed decline of the differentiation efficiency of stem cells remain largely unclear. This study investigated Drosophila midguts and identified an obvious upregulation of caudal ( cad ), which encodes a homeobox transcription factor. This factor is traditionally known as a central regulator of embryonic anterior-posterior body axis patterning. This study reports that depletion of cad in intestinal stem/progenitor cells promotes quiescent intestinal stem cells (ISCs) to become activate and produce enterocytes in the midgut under normal gut homeostasis conditions. However, overexpression of cad results in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, this study suggests that cad prevents intestinal stem/progenitor cell differentiation by modulating the Janus kinase/signal transducers and activators of the transcription pathway and Sox21a-GATAe signaling cascade. Importantly, the reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . This study identified a function of the homeobox gene cad in the modulation of adult stem cell differentiation and suggested a potential gene target for the treatment of age-related diseases induced by age-related stem cell dysfunction.
Adult stem cells undergo an aging-related decline of differentiation efficiency in aged animals. However, the underlying mechanisms that ultimately lead to this observed decline of differentiation efficiency in stem cells still remain largely unclear. By using the Drosophila midgut as a model system, this study identified the homeobox family transcription factor gene caudal ( cad ), the expression of which is significantly upregulated in intestinal stem cells (ISCs) and progenitor cells of aged Drosophila . Depletion of cad promoted quiescent ISCs to become activate and produce enterocytes (ECs) in midguts under normal gut homeostasis conditions; However, overexpression of cad resulted in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, cad prevents ISC-to-EC differentiation by inhibiting JAK/STAT signaling, and the expressions of Sox21a and GATAe . Reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . These findings enable a detailed understanding of the roles of homeobox genes in the modulation of adult stem cell aging in humans. This will be beneficial for the treatment of age-associated diseases that are caused by a functional decline of stem cells.
研究领域:
发育生物学
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干细胞生物学
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衰老研究
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分子遗传学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Gilbert Audira,Jong-Chin Huang,Kelvin H.-C. Chen,Kevin Adi Kurnia,Ross D. Vasquez,Marri Jmelou M. Roldan,Yu-Heng Lai,Chung-Der Hsiao,Cheng-Yo Yen
Recently, the usage of zebrafish for pain studies has increased in the past years, especially due to its robust pain-stimulated behaviors. Fin amputation has been demonstrated to induce a noxious response in zebrafish. However, based on the prior study, although lidocaine, the most used painkiller in zebrafish, has been shown to ameliorate amputated zebrafish behaviors, it still causes some prolonged effects. Therefore, alternative painkillers are always needed to improve the treatment quality of fin-amputated zebrafish. Here, the effects of several analgesics in recovering zebrafish behaviors post-fin amputation were evaluated. From the results, five painkillers were found to have potentially beneficial effects on amputated fish behaviors. Overall, these results aligned with their binding energy level to target proteins of COX-1 and COX-2. Later, based on their sub-chronic effects on zebrafish survivability, indomethacin, and diclofenac were further studied. This combination showed a prominent effect in recovering zebrafish behaviors when administered orally or through waterborne exposure, even with lower concentrations. Next, based on the ELISA in zebrafish brain tissue, although some changes were found in the treated group, no statistical differences were observed in most of the tested biomarkers. However, since heatmap clustering showed a similar pattern between biochemical and behavior endpoints, the minor changes in each biomarker may be sufficient in changing the fish behaviors.
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高影响因子
AQUATIC TOXICOLOGY
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2024
·
IF 4.1
Sijie Zhang,Hao Wang,Yunlong Meng,Mijia Li,Yang Li,Xinhao Ye,Shiyi Duan,Shimei Xiao,Huiqiang Lu,Keyuan Zhong
Wound healing and tissue regeneration are influenced by a variety of factors. Adverse lifestyle habits, such as excessive alcohol consumption, delay wound healing and increase the risk of secondary infections. Ethyl butyrate is a common food additive widely used to enhance the aroma of alcoholic beverages. This additive is generally considered harmless to human health in both industrial and domestic settings. However, the ecotoxicity and its effects on wound healing have not been elucidated. In this study, we used zebrafish as the experimental animal, and the caudal fins were amputated to explore the effects of ethyl butyrate on wound healing and tissue regeneration. The effect of ethyl butyrate on blastema and bone regeneration and its impact on the transcriptional levels of regeneration-related genes and inflammation-related genes were evaluated. RNA-seq was conducted to determine the differentially expressed genes (DEGs) between the treatment and the control groups. KEGG and GO analysis was conducted to explore the functions of DEGs. Significantly enriched GO terms and KEGG pathways were identified to explore the molecular mechanism underlying the inhibition of zebrafish caudal fin regeneration by ethyl butyrate. The results demonstrated that ethyl butyrate significantly inhibited the regeneration of zebrafish caudal fins, including blastema and bone regeneration. Ethyl butyrate exposure significantly downregulated the expression of genes associated with bone and blastema regeneration and inflammation response. KEGG and GO functional analyses revealed that the DEGs were associated with significant enrichment of extracellular matrix-receptor interactions. Ethyl butyrate treatment downregulated the expression of most extracellular matrix-related genes. These findings indicate that ethyl butyrate potentially modulates pathways associated with the structure, adhesion, modification, and degradation of the extracellular matrix, thereby disrupting extracellular matrix remodeling, inhibiting wound inflammation, impairing blastema and bone regeneration and ultimately hindering caudal fin regeneration. In summary, the findings demonstrate that ethyl butyrate disrupts extracellular matrix remodeling and inhibits the regeneration of zebrafish caudal fins. These results provide valuable insights into the rational use of ethyl butyrate and further investigation of wound healing mechanisms.
研究领域:
毒理学
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再生生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
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2026
·
IF 2.3
Shun Zhou,Dong Zheng,Jiaxue Song,Lirong Jiang,Jinlong Dong,Yu Zhang,Jinjing Cao,Yunji Xiu
Pseudocaranx dentex , a precious marine economic fish, is widely distributed in tropical and subtropical seas. However, frequent disease outbreaks have hindered the sustainable development of its aquaculture. In this investigation, the kidney cell line (named PDK) and caudal fin cell line (named PDF) of P. dentex were established and characterized. According to our findings, both cell lines thrived best in L-15 media with 20% fetal bovine serum (FBS) at 26°C. Both cell lines have been stably passaged for more than 40 generations and maintained high viability after cryopreservation in liquid nitrogen. Their origin from P. dentex was confirmed by the COI gene sequencing data. Meanwhile, chromosome analysis demonstrated that PDK and PDF cells shared a modal chromosome number of 48. In addition, both cell lines could be transfected with pEGFP-N3 plasmid via non-liposomal method, indicating potential for in vitro exogenous gene function studies. Furthermore, bacterial susceptibility testing revealed that both cell lines exhibited high sensitivity to Vibrio anguillarum and Vibrio vulnificus . However, PDK cells demonstrated reduced susceptibility to Edwardsiella tarda , while PDF cells showed diminished sensitivity to Vibrio alginolyticus . Virus susceptibility results indicated that PDK cells exhibit greater sensitivity to Micropterus salmoides rhabdovirus (MSRV) than to Red sea bream iridovirus (RSIV), while PDF cells are only susceptible to MSRV but show no response to RSIV. In summary, the PDK and PDF cell lines can serve as key tools for studies on the genetics, cell biology, and immune defence mechanisms of P. dentex , and hold significant value for fish genetics, disease research, and aquaculture disease prevention and control.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Lijun Zhu,Wenjie Huang,Jingjing Shi,Fei Li,Xiuxia Sun,Jianxi Xiao
The degradation of elastin in aged skin results in the loss of elasticity, the formation of wrinkles, and even a reduced ability for wound healing after injury. However, previous studies about elastin material have been limited by high immunogenicity of animal-derived elastin, the use of single elastin peptide sequences, and residual crosslinking agents. In this study, we designed a multipotent anti-aging recombinant human elastin (rElastin) and utilized it to counteract caudal fin shrinkage in zebrafish and D-galactose-induced intrinsic skin aging in mice. The rElastin demonstrated thermoresponsive reversible phase-transition closely resembling that of natural elastin. In vitro , cell experiments demonstrated that rElastin effectively promoted the proliferation, adhesion, and spreading of HFF-1 cells. In a D-galactose-induced intrinsic aging mouse model, rElastin significantly restored dermal density, skin hydration, and TEWL to levels approaching those of healthy skin. Histological analysis further confirmed that rElastin facilitated the deposition of collagen and regeneration of elastic fibers, thereby promoting structural and functional repair of aging skin. Additionally, rElastin obviously inhibited the tail fin shrinkage after UV radiation. rElastin effectively targets skin symptoms associated with intrinsic aging, providing fresh insights into anti-aging therapies and showcasing strong potential for applications in regenerative medicine and cosmetic dermatology.
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PubMed
高影响因子
AQUACULTURE RESEARCH
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2023
·
IF 2
Tingting Hou,Zaizhao Wang,Kui Tang,Shuai Zhang,Shilin Liu,Jialiang Liu,Xiaoteng Fan,Xiaolin Liu
This study investigated the capability for fin regeneration in zebrafish larvae with the mechanism of FCS isolated from green and purple sea cucumbers Apostichopus japonicus (G-FCS and P-FCS). HPGPC determined that mean molecular weight of purified G-FCS and P-FCS is 19.5 and 18.8 kDa, and the FT-IR spectrum displayed similar characteristic absorption peaks. AFM images presented that G-FCS was shown as a spherical polysaccharide, while P-FCS molecules exhibited elongated chains. For the regeneration examination, FCS increased the regrowth area of the larval fin at 48 hours postamputation with enhanced locomotor behaviors, and the transcription levels of regeneration-related genes (Wnt10a, msx1b, fgf20a, bmp2a, bmp4, and igf2b) were upregulated. Moreover, FCS promoted the mRNA expression of inflammatory factors (iNOS, TNF-α, IL-6, IL-10, and IFN-γ) and TLR/NF-κB pathway-related genes (TLR3, TLR4a, NF-κb, and MyD88). The Western blot analyses of TNF-α and IL-1β supported that FCS enhanced immune response. ELISA results indicated that FCSs increased the contents of NO, CAT, SOD, and G6PD. Summarily, the present results suggested that FCS was a potential regeneration enhancer by elevating immunomodulatory and antioxidative processes in zebrafish.
研究领域:
海洋生物学
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发育生物学
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免疫学
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生物化学
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DOI
高影响因子
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