scholarly journals Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 147
Author(s):  
Phatchanat Klaihmon ◽  
Chanchao Lorthongpanich ◽  
Pakpoom Kheolamai ◽  
Sudjit Luanpitpong ◽  
Surapol Issaragrisil
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Chemotherapeutic Agents ◽  
Human Lung Cancer ◽  
Hippo Signaling ◽  
Loss Of Function ◽  
Endothelial Progenitor ◽  
Cell Functions ◽  
Human Lung Cancer Cells ◽  
Angiogenic Genes

The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.

miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells

2015 ◽  
Vol 396 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Sebastian M. Goerke ◽  
Lena S. Kiefer ◽  
G. Björn Stark ◽  
Filip Simunovic ◽  
Günter Finkenzeller
Keyword(s):  
Tissue Engineering ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Growth Parameters ◽  
Therapeutic Option ◽  
Tube Formation ◽  
Loss Of Function ◽  
Endothelial Progenitor

Abstract Vascularization plays an important role in tissue engineering applications. It is known that implantation of differentiated endothelial cells or endothelial progenitor cells (EPCs) from cord blood (cbEPCs) gives rise to the formation of a complex functional neovasculature, whereas EPCs isolated from peripheral blood (pbEPCs) have a limited capability to form blood vessels upon implantation. MicroRNA-126 (miR-126) has been shown to have pro-angiogenic effects in vivo. In this study, we investigated whether modulation of miR-126 expression in pbEPCs may alter their angiogenic properties. Gain of function and loss of function experiments revealed that miR-126 has anti-angiogenic effects in pbEPCs. Overexpression of miR-126 resulted in decreased proliferation, migration, invasion and tube formation, while inhibition of miR-126 induced the opposite effects. However, modulation of miR-126 expression did not influence apoptotic susceptibility of pbEPCs. This study provides evidence that inhibition of miR-126 improves angiogenesis-related growth parameters in pbEPCs and may represent a therapeutic option to ameliorate the angiogenic and vasculogenic properties of pbEPCs.

scholarly journals Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Ding Tian ◽  
Yin Xiang ◽  
Yong Tang ◽  
Zhuowang Ge ◽  
Qianhui Li ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
High Glucose ◽  
Vascular Complications ◽  
Limb Ischemia ◽  
Underlying Mechanism ◽  
Circular Rnas ◽  
High Concentration ◽  
Endothelial Progenitor ◽  
Cell Functions

Abstract Dysfunction of endothelial progenitor cells (EPCs) is a key factor in vascular complications of diabetes mellitus. Although the roles of microRNAs and circular RNAs in regulating cell functions have been thoroughly studied, their role in regulating autophagy and apoptosis of EPCs remains to be elucidated. This study investigated the roles of mir-20a-5p and its predicted target circ-ADAM9 in EPCs treated with high glucose (30 mM) and in a diabetic mouse hind limb ischemia model. It is found that Mir-20a-5p inhibited autophagy and apoptosis of EPCs induced by high-concentration glucose. Further, mir-20a-5p could inhibit the expression of PTEN and ATG7 in EPCs, and promote the phosphorylation of AKT and mTOR proteins under high-glucose condition. Investigation of the underlying mechanism revealed that circ-ADAM9, as a miRNA sponges of mir-20a-5p, promoted autophagy and apoptosis of EPCs induced by high-concentration glucose. Circ-ADAM9 upregulated PTEN and ATG7 in interaction with mir-20a-5p, and inhibited the phosphorylation of AKT and mTOR to aggravate autophagy and apoptosis of EPCs under high glucose. In addition, silencing of circ-ADAM9 increased microvessel formation in the hind limbs of diabetic mice. Our findings disclose a novel autophagy/apoptosis-regulatory pathway that is composed of mir-20a-5p, circ-ADAM9, PTEN, and ATG7. Circ-ADAM9 is a potential novel target for regulating the function of diabetic EPCs and angiogenesis.

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