Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications

Neurotrophic factor 3 (NT-3), a potent neurotrophin, promotes neuronal survival and axonal regeneration while demonstrating a unique capacity to induce lineage-specific differentiation of pluripotent stem cells into functional neurons, underscoring its therapeutic potential in neural repair. Despite...

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Main Authors: Wenjing Geng, Liang Lu, Tangmin Li, Mingyi Zhou, Wei Chen, Hao Tan, Debin Zhong, Guanwang Shen, Ping Lin, Qingyou Xia, Ping Zhao, Zhiqing Li
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Insects
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Online Access:https://www.mdpi.com/2075-4450/16/7/676
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author Wenjing Geng
Liang Lu
Tangmin Li
Mingyi Zhou
Wei Chen
Hao Tan
Debin Zhong
Guanwang Shen
Ping Lin
Qingyou Xia
Ping Zhao
Zhiqing Li
author_facet Wenjing Geng
Liang Lu
Tangmin Li
Mingyi Zhou
Wei Chen
Hao Tan
Debin Zhong
Guanwang Shen
Ping Lin
Qingyou Xia
Ping Zhao
Zhiqing Li
author_sort Wenjing Geng
collection DOAJ
description Neurotrophic factor 3 (NT-3), a potent neurotrophin, promotes neuronal survival and axonal regeneration while demonstrating a unique capacity to induce lineage-specific differentiation of pluripotent stem cells into functional neurons, underscoring its therapeutic potential in neural repair. Despite these advantages, the large-scale production of recombinant human NT-3 with preserved structure integrity and functional bioactivity remains a critical challenge. This study takes advantage of the silk gland bioreactor of silkworms for the recombinant expression of human NT-3 protein on a large scale. Our findings reveal that NT-3 was successfully expressed in the middle silk gland of silkworms and secreted into the silk fibers, achieving a yield of up to 0.5 mg of bioactive NT-3 per gram of cocoon weight. The engineered NT-3-functionalized silk material demonstrates no cytotoxicity and significantly enhanced the proliferation, migration, and differentiation of neural cells compared to natural silk protein. Importantly, this functionalized material also promotes neurite outgrowth in HT-22 cells. These results collectively underscore the high bioactivity of the recombinant human NT-3 protein produced in the silkworm silk gland. The ongoing fabrication of NT-3-incorporated silk-based materials holds considerable promise for advancing tissue engineering and nerve regeneration applications.
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spelling doaj-art-7765dec9ab7546e8a532a304e511906f2025-08-20T03:35:37ZengMDPI AGInsects2075-44502025-06-0116767610.3390/insects16070676Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical ApplicationsWenjing Geng0Liang Lu1Tangmin Li2Mingyi Zhou3Wei Chen4Hao Tan5Debin Zhong6Guanwang Shen7Ping Lin8Qingyou Xia9Ping Zhao10Zhiqing Li11Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaCentury Legend Biotechnology Research Institute (Chongqing) Co., Ltd., Chongqing 402160, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City & Southwest University, Biological Science Research Center, Southwest University, Chongqing 400715, ChinaNeurotrophic factor 3 (NT-3), a potent neurotrophin, promotes neuronal survival and axonal regeneration while demonstrating a unique capacity to induce lineage-specific differentiation of pluripotent stem cells into functional neurons, underscoring its therapeutic potential in neural repair. Despite these advantages, the large-scale production of recombinant human NT-3 with preserved structure integrity and functional bioactivity remains a critical challenge. This study takes advantage of the silk gland bioreactor of silkworms for the recombinant expression of human NT-3 protein on a large scale. Our findings reveal that NT-3 was successfully expressed in the middle silk gland of silkworms and secreted into the silk fibers, achieving a yield of up to 0.5 mg of bioactive NT-3 per gram of cocoon weight. The engineered NT-3-functionalized silk material demonstrates no cytotoxicity and significantly enhanced the proliferation, migration, and differentiation of neural cells compared to natural silk protein. Importantly, this functionalized material also promotes neurite outgrowth in HT-22 cells. These results collectively underscore the high bioactivity of the recombinant human NT-3 protein produced in the silkworm silk gland. The ongoing fabrication of NT-3-incorporated silk-based materials holds considerable promise for advancing tissue engineering and nerve regeneration applications.https://www.mdpi.com/2075-4450/16/7/676human neurotrophic factor 3biosynthesissilk materialssilkworm
spellingShingle Wenjing Geng
Liang Lu
Tangmin Li
Mingyi Zhou
Wei Chen
Hao Tan
Debin Zhong
Guanwang Shen
Ping Lin
Qingyou Xia
Ping Zhao
Zhiqing Li
Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
Insects
human neurotrophic factor 3
biosynthesis
silk materials
silkworm
title Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
title_full Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
title_fullStr Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
title_full_unstemmed Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
title_short Biosynthesis of Bioactive Human Neurotrophic Factor 3 in Silkworms and Its Biomedical Applications
title_sort biosynthesis of bioactive human neurotrophic factor 3 in silkworms and its biomedical applications
topic human neurotrophic factor 3
biosynthesis
silk materials
silkworm
url https://www.mdpi.com/2075-4450/16/7/676
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