Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice
Chronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in <i>Escherichia col...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/9/12/734 |
| _version_ | 1797461428563607552 |
|---|---|
| author | Yunxian Li Shixin Lin Sheng Xiong Qiuling Xie |
| author_facet | Yunxian Li Shixin Lin Sheng Xiong Qiuling Xie |
| author_sort | Yunxian Li |
| collection | DOAJ |
| description | Chronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in <i>Escherichia coli</i> BL21 (DE3) and demonstrate its efficacy on dermal wounds in streptozotocin (STZ)-induced diabetic and nondiabetic mice by the dorsal incisional skin wound model. Results revealed that the rhmatIL-33 accelerated the scratch-healing of keratinocytes and fibroblasts at the cellular level. The wounds of diabetic mice (DM) showed more severe ulceration and inflammation than wild-type mice (WT), and the exogenous administration of rhmatIL-33 increased wound healing in both diabetic and wild-type mice. Compared with the up-regulation of endogenous IL-33 mRNA after injury in WT mice, the IL-33 mRNA decreased after injury in DM mice. Exogenous IL-33 administration increased the endogenous IL-33 mRNA in the DM group but decreased the IL-33 mRNA expression level of the WT group, indicating that IL-33 plays a balancing role in wound healing. IL-33 administration also elevated ILC2 cells in the wounds of diabetic and non-diabetic mice and improve the transcript levels of YM1, a marker of M2 macrophages. In conclusion, Hyperglycemia in diabetic mice inhibited the expression of IL-33 in the dermal wound. Exogenous addition of recombinant IL-33 promoted wound healing in diabetic mice by effectively increasing the level of IL-33 in wound tissue, increasing ILC2 cells, and accelerating the transformation of macrophage M1 to M2 phenotype. |
| first_indexed | 2024-03-09T17:19:17Z |
| format | Article |
| id | doaj.art-8962fa7357fc4c72b2647b7527d9cdff |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-09T17:19:17Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-8962fa7357fc4c72b2647b7527d9cdff2023-11-24T13:20:04ZengMDPI AGBioengineering2306-53542022-11-0191273410.3390/bioengineering9120734Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic MiceYunxian Li0Shixin Lin1Sheng Xiong2Qiuling Xie3College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaCollege of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaCollege of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaCollege of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaChronic refractory wounds are one of the complications of diabetes mellitus that require effective therapy. The dermal-wound-healing property of IL-33 in diabetics is little understood. Therefore, this study aimed to express recombinant humanized mature IL-33 (rhmatIL-33) in <i>Escherichia coli</i> BL21 (DE3) and demonstrate its efficacy on dermal wounds in streptozotocin (STZ)-induced diabetic and nondiabetic mice by the dorsal incisional skin wound model. Results revealed that the rhmatIL-33 accelerated the scratch-healing of keratinocytes and fibroblasts at the cellular level. The wounds of diabetic mice (DM) showed more severe ulceration and inflammation than wild-type mice (WT), and the exogenous administration of rhmatIL-33 increased wound healing in both diabetic and wild-type mice. Compared with the up-regulation of endogenous IL-33 mRNA after injury in WT mice, the IL-33 mRNA decreased after injury in DM mice. Exogenous IL-33 administration increased the endogenous IL-33 mRNA in the DM group but decreased the IL-33 mRNA expression level of the WT group, indicating that IL-33 plays a balancing role in wound healing. IL-33 administration also elevated ILC2 cells in the wounds of diabetic and non-diabetic mice and improve the transcript levels of YM1, a marker of M2 macrophages. In conclusion, Hyperglycemia in diabetic mice inhibited the expression of IL-33 in the dermal wound. Exogenous addition of recombinant IL-33 promoted wound healing in diabetic mice by effectively increasing the level of IL-33 in wound tissue, increasing ILC2 cells, and accelerating the transformation of macrophage M1 to M2 phenotype.https://www.mdpi.com/2306-5354/9/12/734IL-33diabetic wound healingM2 macrophagesILC2 cells |
| spellingShingle | Yunxian Li Shixin Lin Sheng Xiong Qiuling Xie Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice Bioengineering IL-33 diabetic wound healing M2 macrophages ILC2 cells |
| title | Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice |
| title_full | Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice |
| title_fullStr | Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice |
| title_full_unstemmed | Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice |
| title_short | Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice |
| title_sort | recombinant expression of human il 33 protein and its effect on skin wound healing in diabetic mice |
| topic | IL-33 diabetic wound healing M2 macrophages ILC2 cells |
| url | https://www.mdpi.com/2306-5354/9/12/734 |
| work_keys_str_mv | AT yunxianli recombinantexpressionofhumanil33proteinanditseffectonskinwoundhealingindiabeticmice AT shixinlin recombinantexpressionofhumanil33proteinanditseffectonskinwoundhealingindiabeticmice AT shengxiong recombinantexpressionofhumanil33proteinanditseffectonskinwoundhealingindiabeticmice AT qiulingxie recombinantexpressionofhumanil33proteinanditseffectonskinwoundhealingindiabeticmice |