Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells
Mesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been repo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.796744/full |
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| author | Shuping Yan Pingsheng Ye Muhammad Tahir Aleem Xi Chen Nana Xie Yuanshu Zhang |
| author_facet | Shuping Yan Pingsheng Ye Muhammad Tahir Aleem Xi Chen Nana Xie Yuanshu Zhang |
| author_sort | Shuping Yan |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been reported in animal mastitis. We hypothesized that MSCs overexpressing ACE2 is more effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory injury in mammary epithelial cells compared to MSCs alone. The results showed that MSC-ACE2 inhibited the LPS induction by upregulation of TNF-α, IL-Iβ, IL-6, and iNOS mRNA expression levels in EpH4-Ev cells compared with MSCs. Furthermore, results showed that both MSC and MSC-ACE2 were significantly activated IL-10/STAT3/SOCS3 signaling pathway as well as inhibited TLR4/NF-κB and MAPK signaling pathways, but MSC-ACE2 had more significant effects. Meanwhile, MSC-ACE2 promoted the expression of proliferation-associated proteins and inhibited the expression of the apoptosis-associated proteins in EpH4-Ev cells. In addition, MSC and MSC-ACE2 reversed the LPS-induced downregulation expression levels of the tight junction proteins in mammary epithelial cells, indicating that both MSC as well as MSC-ACE2 could promote blood-milk barrier repair, and MSC-ACE2 was more effective. These results suggested that MSCs overexpressing ACE2 were more anti-inflammatory as well as anti-injurious action into LPS-induced inflammatory injury in the EpH4-Ev cells. Thus, MSCs overexpressing ACE2 is expected to serve as a potential strategy for mastitis treatment. |
| first_indexed | 2024-04-11T17:25:55Z |
| format | Article |
| id | doaj.art-9694bdb917de488083e40bf61f057247 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T17:25:55Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9694bdb917de488083e40bf61f0572472022-12-22T04:12:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.796744796744Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial CellsShuping Yan0Pingsheng Ye1Muhammad Tahir Aleem2Xi Chen3Nana Xie4Yuanshu Zhang5Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaMinistry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaMesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been reported in animal mastitis. We hypothesized that MSCs overexpressing ACE2 is more effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory injury in mammary epithelial cells compared to MSCs alone. The results showed that MSC-ACE2 inhibited the LPS induction by upregulation of TNF-α, IL-Iβ, IL-6, and iNOS mRNA expression levels in EpH4-Ev cells compared with MSCs. Furthermore, results showed that both MSC and MSC-ACE2 were significantly activated IL-10/STAT3/SOCS3 signaling pathway as well as inhibited TLR4/NF-κB and MAPK signaling pathways, but MSC-ACE2 had more significant effects. Meanwhile, MSC-ACE2 promoted the expression of proliferation-associated proteins and inhibited the expression of the apoptosis-associated proteins in EpH4-Ev cells. In addition, MSC and MSC-ACE2 reversed the LPS-induced downregulation expression levels of the tight junction proteins in mammary epithelial cells, indicating that both MSC as well as MSC-ACE2 could promote blood-milk barrier repair, and MSC-ACE2 was more effective. These results suggested that MSCs overexpressing ACE2 were more anti-inflammatory as well as anti-injurious action into LPS-induced inflammatory injury in the EpH4-Ev cells. Thus, MSCs overexpressing ACE2 is expected to serve as a potential strategy for mastitis treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2021.796744/fullACE2MSCsEpH4-Ev cells injuryIL-10/STAT3/SOCS3 signaling pathwayblood-milk barrier |
| spellingShingle | Shuping Yan Pingsheng Ye Muhammad Tahir Aleem Xi Chen Nana Xie Yuanshu Zhang Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells Frontiers in Immunology ACE2 MSCs EpH4-Ev cells injury IL-10/STAT3/SOCS3 signaling pathway blood-milk barrier |
| title | Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells |
| title_full | Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells |
| title_fullStr | Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells |
| title_full_unstemmed | Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells |
| title_short | Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells |
| title_sort | mesenchymal stem cells overexpressing ace2 favorably ameliorate lps induced inflammatory injury in mammary epithelial cells |
| topic | ACE2 MSCs EpH4-Ev cells injury IL-10/STAT3/SOCS3 signaling pathway blood-milk barrier |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.796744/full |
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