E3 ligase activity of Carboxyl terminus of Hsc70 interacting protein (CHIP) in Wharton's jelly derived mesenchymal stem cells improves their persistence under hyperglycemic stress and promotes the prophylactic effects against diabetic cardiac damages

被引：22

作者：

Ali, Ayaz ^{[1
]}

Kuo, Wei-Wen ^{[1
,2
]}

Kuo, Chia-Hua ^{[3
]}

Lo, Jeng-Fan ^{[4
]}

Chen, Michael Y. C. ^{[5
]}

Daddam, Jayasimha R. ^{[6
]}

Ho, Tsung-Jung ^{[7
,8
]}

Viswanadha, Vijaya Padma ^{[9
]}

Shibu, Marthandam Asokan ^{[6
]}

Huang, Chih-Yang ^{[6
,10
,11
,12
,13
]}

机构：

[1] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan

[2] China Med Univ, PhD Program Biotechnol Ind, Taichung, Taiwan

[3] Univ Taipei, Lab Exercise Biochem, Taipei, Taiwan

[4] Natl Yang Ming Univ, Inst Oral Biol, Taipei, Taiwan

[5] Buddhist Tzu Chi Gen Hosp, Dept Cardiol, Hualien, Taiwan

[6] Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Cardiovasc & Mitochondria Related Dis Res Ctr, Hualien, Taiwan

[7] Tzu Chi Univ, Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Chinese Med, Hualien, Taiwan

[8] Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Integrat Ctr Tradit Chinese & Modern Med, Hualien, Taiwan

[9] Bharathiar Univ, Dept Biotechnol, Coimbatore, Tamil Nadu, India

[10] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan

[11] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung, Taiwan

[12] Asia Univ, Dept Biotechnol, Taichung, Taiwan

[13] Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ, Hualien, Taiwan

来源：

BIOENGINEERING & TRANSLATIONAL MEDICINE | 2021年 / 6卷 / 03期

关键词：

apoptosis; carboxyl terminus of Hsc70 interacting protein; diabetes; phosphatase and tensin homolog; Wharton's jelly derived mesenchymal stem cells; CARDIOVASCULAR-DISEASE; C-TERMINUS; PTEN; DYSFUNCTION; APOPTOSIS; DEGRADATION; EXPRESSION; CARDIOMYOPATHY; GENERATION; INFARCTION;

D O I：

10.1002/btm2.10234

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated. In this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased Carboxyl terminus of Hsc70 interacting protein (CHIP) expression promoted phosphatase and tensin homolog (PTEN) degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Coculturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in embryo derived cardiac cell lines. CHIP overexpressing and PTEN silenced WJMSCs ameliorated diabetic effects in streptozotocin (STZ) induced diabetic rats and further improved their body weight and heart weight, and rescued from hyperglycemia-induced cardiac injury. Considering these, the current study suggests that CHIP confers resistance to apoptosis and acts as a potentiation factor in WJMSCs to provide protection from degenerative effects of diabetes.

引用

页数：17

共 52 条

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