Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal
Abstract Background Stem cell therapies may potentially be used in regenerative and reconstructive medicine due to their ability for self-renewal and differentiation. Stressful conditions, such as hyperglycemia, adversely affect stem cell functions, impairing their function and promoting differentia...
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BMC
2025-04-01
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| Online Access: | https://doi.org/10.1186/s40659-025-00604-7 |
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| author | Ayaz Ali Wei-Wen Kuo Chia-Hua Kuo Jeng-Feng Lo Dennis Jine-Yuan Hsieh Peiying Pai Tsung-Jung Ho Marthandam Asokan Shibu Shinn-Zong Lin Chih-Yang Huang |
| author_facet | Ayaz Ali Wei-Wen Kuo Chia-Hua Kuo Jeng-Feng Lo Dennis Jine-Yuan Hsieh Peiying Pai Tsung-Jung Ho Marthandam Asokan Shibu Shinn-Zong Lin Chih-Yang Huang |
| author_sort | Ayaz Ali |
| collection | DOAJ |
| description | Abstract Background Stem cell therapies may potentially be used in regenerative and reconstructive medicine due to their ability for self-renewal and differentiation. Stressful conditions, such as hyperglycemia, adversely affect stem cell functions, impairing their function and promoting differentiation by opposing self-renewal. The carboxyl terminus of HSP70 interacting protein (CHIP), which is a cochaperone and E3 ligase, maintains protein homeostasis and performs quality control of the cell via ubiquitylation. However, the role of CHIP in regulating stemness remains unknown. Results Hyperglycemia downregulated CHIP-induced p53, arrested the cell cycle at the gap (G1) phase, and promoted the loss of stemness in WJMSCs. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and cell cycle analysis showed that CHIP-overexpressing WJMSCs downregulated the expression of phosphorylated p53 and shortened its half-life while enhancing self-renewal factors. Additionally, co-IP and Western blotting revealed that CHIP promoted the ubiquitination and proteasomal degradation of hyperglycemia-induced p53 through the chaperone system. Conclusions CHIP may promote ubiquitin-mediated proteasomal degradation of hyperglycemia-induced p53 rescues self-renewal genes, which can maintain the long-term undifferentiated state of WJMSCs. CHIP may be an alternative therapeutic option in regenerative medicine for hyperglycemic-related complications in diabetes. |
| format | Article |
| id | doaj-art-e5b8d937082c40a5947a7ecec0ee249d |
| institution | OA Journals |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | Biological Research |
| spelling | doaj-art-e5b8d937082c40a5947a7ecec0ee249d2025-08-20T02:30:20ZengBMCBiological Research0717-62872025-04-0158111110.1186/s40659-025-00604-7Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewalAyaz Ali0Wei-Wen Kuo1Chia-Hua Kuo2Jeng-Feng Lo3Dennis Jine-Yuan Hsieh4Peiying Pai5Tsung-Jung Ho6Marthandam Asokan Shibu7Shinn-Zong Lin8Chih-Yang Huang9Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, University of AberdeenDepartment of Biological Science and Technology, China Medical UniversityLaboratory of Exercise Biochemistry, University of TaipeiInstitute of Oral Biology, National Yang-Ming UniversitySchool of Medical Technology, Chung Shan Medical UniversitySchool of Medicine, College of Medicine, China Medical UniversityDepartment of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi UniversityDepartment of Biotechnology, Bharathiar UniversityBioinnovation Center, Buddhist Tzu Chi Medical FoundationGraduate Institute of Biomedical Sciences, China Medical UniversityAbstract Background Stem cell therapies may potentially be used in regenerative and reconstructive medicine due to their ability for self-renewal and differentiation. Stressful conditions, such as hyperglycemia, adversely affect stem cell functions, impairing their function and promoting differentiation by opposing self-renewal. The carboxyl terminus of HSP70 interacting protein (CHIP), which is a cochaperone and E3 ligase, maintains protein homeostasis and performs quality control of the cell via ubiquitylation. However, the role of CHIP in regulating stemness remains unknown. Results Hyperglycemia downregulated CHIP-induced p53, arrested the cell cycle at the gap (G1) phase, and promoted the loss of stemness in WJMSCs. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and cell cycle analysis showed that CHIP-overexpressing WJMSCs downregulated the expression of phosphorylated p53 and shortened its half-life while enhancing self-renewal factors. Additionally, co-IP and Western blotting revealed that CHIP promoted the ubiquitination and proteasomal degradation of hyperglycemia-induced p53 through the chaperone system. Conclusions CHIP may promote ubiquitin-mediated proteasomal degradation of hyperglycemia-induced p53 rescues self-renewal genes, which can maintain the long-term undifferentiated state of WJMSCs. CHIP may be an alternative therapeutic option in regenerative medicine for hyperglycemic-related complications in diabetes.https://doi.org/10.1186/s40659-025-00604-7Carboxyl terminus of HSP70 interacting proteinp53HyperglycemiaSelf-renewalMesenchymal stem cells |
| spellingShingle | Ayaz Ali Wei-Wen Kuo Chia-Hua Kuo Jeng-Feng Lo Dennis Jine-Yuan Hsieh Peiying Pai Tsung-Jung Ho Marthandam Asokan Shibu Shinn-Zong Lin Chih-Yang Huang Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal Biological Research Carboxyl terminus of HSP70 interacting protein p53 Hyperglycemia Self-renewal Mesenchymal stem cells |
| title | Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal |
| title_full | Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal |
| title_fullStr | Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal |
| title_full_unstemmed | Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal |
| title_short | Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal |
| title_sort | chaperone assisted e3 ligase engineered mesenchymal stem cells target hyperglycemia induced p53 for ubiquitination and proteasomal degradation ameliorates self renewal |
| topic | Carboxyl terminus of HSP70 interacting protein p53 Hyperglycemia Self-renewal Mesenchymal stem cells |
| url | https://doi.org/10.1186/s40659-025-00604-7 |
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