基因组信息指导下仿刺参来源具有修复功能的活性肽的挖掘及活性评价

doi:10.3976/j.issn.1002-4026.20260052

Abstract

Abstract: Wound healing is a key physiological process for functional repair and recovery following tissue injury, involving a series of complex biological mechanisms initiated by damage. Affected by multiple factors such as the individual’s physical condition, wound size and severity, and the presence of concurrent infection, wound repair often requires medical intervention. In particular, the healing process of chronic wounds often fails to achieve ideal therapeutic outcomes, thereby placing an increasingly heavy burden on the socioeconomic systems and healthcare services. Compared with conventional drugs, natural bioactive peptides exhibit advantages such as low side effects, low immunogenicity, low toxicity, favorable physiological functions, good cell permeability, and high biodiversity, demonstrating great potential as next-generation healing agents. As an important organism for research on wound healing and tissue regeneration, sea cucumbers possess remarkable regenerative capabilities and serve as a valuable model organism for related studies. In this study, the growth factor Sh‑EGFl‑1 derived from Stichopus horrens was used as a probe to screen the genome of Apostichopus japonicus. A homologous sequence, DE37, was identified through local BLAST alignment and subsequently synthesized chemically. Circular dichroism spectroscopy revealed that the secondary structure of DE37 consisted of 3.7% α-helix, 41.1% β-sheet, 21.5% β-turn, and 33.6% random coil. Cell experiments showed that 50 µmol/L DE37 effectively promoted the proliferation and migration of HaCaT cells. DE37 at 5 µmol/L and 10 µmol/L significantly enhanced the proliferation and migration of L929 cells, with the 10 μmol/L group showing the most pronounced effect, increasing the proliferation rate by 39.39%. In addition, it accelerated cell migration, improving the wound healing rate by 26.97%. Further molecular docking was performed to predict the binding pocket and key amino acid residues involved in the interaction between the active peptide DE37 and the receptor EGFR.

Key words: Apostichopus japonicus, bioactive peptides, cell proliferation, cell migration, molecular docking

CLC Number:

Q516

CHEN Xinhua, WANG Weitao, YIN Xin, ZHANG Lixin, MENG Yiwei, XIA Xuekui. Genome-guided discovery and bioactivity evaluation of repair-promoting peptides from Apostichopus japonicus[J].Shandong Science, 0, (): 1-.

References

[1] LEE S H, JEONG S K, AHN S K. An update of the defensive barrier function of skin[J]. Yonsei Medical Journal, 2006, 47(3): 293. DOI:10.3349/ymj.2006.47.3.293.

[2] RAHIM K, SALEHA S, ZHU X D, et al. Bacterial contribution in chronicity of wounds[J]. Microbial Ecology, 2017, 73(3): 710-721. DOI:10.1007/s00248-016-0867-9.

[3] SITUM M, KOLIĆ M, REDZEPI G, et al. Chronic wounds as a public health problem[J]. Acta Medica Croatica, 2014, 68(Suppl 1): 5-7.

[4] NUSSBAUM S R, CARTER M J, FIFE C E, et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds[J]. Value in Health, 2018, 21(1): 27-32. DOI:10.1016/j.jval.2017.07.007.

[5] BEENKEN A, MOHAMMADI M. The FGF family: Biology, pathophysiology and therapy[J]. Nature Reviews Drug Discovery, 2009, 8(3): 235-253. DOI:10.1038/nrd2792.

[6] BROADLEY K N, AQUINO A M, WOODWARD S C, et al. Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair[J]. Laboratory Investigation; a Journal of Technical Methods and Pathology, 1989, 61(5): 571-575.

[7] MONTESANO R, VASSALLI J D, BAIRD A, et al. Basic fibroblast growth factor induces angiogenesisin vitro[J]. Proceedings of the National Academy of Sciences of the United States of America, 1986, 83(19): 7297-7301. DOI:10.1073/pnas.83.19.7297.

[8] SHIRAKATA Y, KIMURA R, NANBA D, et al. Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing[J]. Journal of Cell Science, 2005, 118(11): 2363-2370. DOI:10.1242/jcs.02346.

[9] NANBA D, TOKI F, BARRANDON Y, et al. Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation[J]. Journal of Dermatological Science, 2013, 72(2): 81-86. DOI:10.1016/j.jdermsci.2013.05.009.

[10] WERNER S, GROSE R. Regulation of wound healing by growth factors and cytokines[J]. Physiological Reviews, 2003, 83(3): 835-870. DOI:10.1152/physrev.2003.83.3.835.

[11] MEI TEH B, REDMOND S L, SHEN Y, et al. TGF-α/HA complex promotes tympanic membrane keratinocyte migration and proliferationviaErbB1 receptor[J]. Experimental Cell Research, 2013, 319(6): 790-799. DOI:10.1016/j.yexcr.2013.01.015.

[12] SEBOLT-LEOPOLD J S, HERRERA R. Targeting the mitogen-activated protein kinase cascade to treat cancer[J]. Nature Reviews Cancer, 2004, 4(12): 937-947. DOI:10.1038/nrc1503.

[13] PILUS N S M, MUHAMAD A, SHAHIDAN M A, et al. Potential of epidermal growth factor-like peptide from the sea cucumberStichopus horrensto increase the growth of human cells: In silico molecular docking approach[J]. Marine Drugs, 2022, 20(10): 596. DOI:10.3390/md20100596.

[14] YANG J Y, ZHANG Y. I-TASSER server: New development for protein structure and function predictions[J]. Nucleic Acids Research, 2015, 43(W1): W174-W181. DOI:10.1093/nar/gkv342.

[15] WATERHOUSE A, BERTONI M, BIENERT S, et al. SWISS-MODEL: Homology modelling of protein structures and complexes[J]. Nucleic Acids Research, 2018, 46(W1): W296-W303. DOI:10.1093/nar/gky427.

[16] GREENFIELD N J. Using circular dichroism spectra to estimate protein secondary structure[J]. Nature Protocols, 2006, 1(6): 2876-2890. DOI:10.1038/nprot.2006.202.

[17] ZHANG Z J, ZHANG S S, NIU B L, et al. A determining factor for insect feeding preference in the silkworm,Bombyx mori[J]. PLoS Biology, 2019, 17(2): e3000162. DOI:10.1371/journal.pbio.3000162.

[18] 张志芹, 蔡芳瑗, 邓勇科, 等. 海参活性肽的制备、分离纯化及生物活性研究进展[J]. 食品工业科技, 2025, 46(24): 483-491. DOI:10.13386/j.issn1002-0306.2025010012.

[19] SUN L N, JIANG C X, SU F, et al. Chromosome-level genome assembly of the sea cucumberApostichopus japonicus[J]. Scientific Data, 2023, 10: 454. DOI:10.1038/s41597-023-02368-9.

[20] GAO L, ZHOU T T, YUAN J, et al. AI-poweredde novoarchitecturing of marine-mimetic antioxidant peptides in yeast synbio factories[J]. Chemical Engineering Journal, 2025, 524: 169604. DOI:10.1016/j.cej.2025.169604.

[21] CHIU J, DAWES I W. Redox control of cell proliferation[J]. Trends in Cell Biology, 2012, 22(11): 592-601. DOI:10.1016/j.tcb.2012.08.002.

[22] WEE P, WANG Z X. Epidermal growth factor receptor cell proliferation signaling pathways[J]. Cancers, 2017, 9(5): 52. DOI:10.3390/cancers9050052.

[23] OGISO H, ISHITANI R, NUREKI O, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains[J]. Cell, 2002, 110(6): 775-787. DOI:10.1016/S0092-8674(02)00963-7.

[24] KOIDE H, MUTO Y, KASAI H, et al. Recognition of an antiparallel β-sheet structure of human epidermal growth factor by its receptor Site-directed mutagenesis studies ofAla-30 and Asn-32[J]. FEBS Letters, 1992, 302(1): 39-42. DOI:10.1016/0014-5793(92)80279-P.

[25] KASZUBA K, GRZYBEK M, ORŁOWSKI A, et al. N-Glycosylation as determinant of epidermal growth factor receptor conformation in membranes[J]. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(14): 4334-4339.

[26] ZHANG Z Y, BOYLE P C, LU B Y, et al. Entropic folding pathway of human epidermal growth factor explored by disulfide scrambling and amplified collective motion simulations,[J]. Biochemistry, 2006, 45(51): 15269-15278.

[27] SHANG J, YE G, SHI K, et al. Structural basis of receptor recognition by SARS-CoV-2[J]. Nature, 2020, 581(7807): 221-224. DOI:10.1038/s41586-020-2179-y.

[28] LAI Y X, WU J C, TAN T H, et al. Engineered exosomes co-delivering EGF and FGF ameliorate androgenetic alopecia in a mouse model[J]. International Journal of Nanomedicine, 2026, 21: 572518. DOI:10.2147/IJN.S572518.

[39] BROECKER M, HAMMER J, DERWAHL M. Excessive activation of tyrosine kinases leads to inhibition of proliferation in a thyroid carcinoma cell line[J]. Life Sciences, 1998, 63(26): 2373-2386. DOI:10.1016/S0024-3205(98)00526-8.

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Genome-guided discovery and bioactivity evaluation of repair-promoting peptides from Apostichopus japonicus

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