Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis
Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this stu...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X2100253X |
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| author | Yaru Guo Feng Mei Ying Huang Siqin Ma Yan Wei Xuehui Zhang Mingming Xu Ying He Boon Chin Heng Lili Chen Xuliang Deng |
| author_facet | Yaru Guo Feng Mei Ying Huang Siqin Ma Yan Wei Xuehui Zhang Mingming Xu Ying He Boon Chin Heng Lili Chen Xuliang Deng |
| author_sort | Yaru Guo |
| collection | DOAJ |
| description | Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this study, we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues. Stiffened matrix promoted sprouting from endothelial cell (EC) spheroids and upregulated expressions of tip cell-enriched genes in vitro. Moreover, tip cells showed increased cellular stiffness, more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs. We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state. YAP is subsequently activated and translocated into nucleus, leading to increased tip cell specification. p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification. Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis, shedding light on the role of mechanotransduction in tip cell formation. This is of special significance in biomaterial design and treatment of some pathological situations. |
| first_indexed | 2024-04-24T08:27:01Z |
| format | Article |
| id | doaj.art-7e27a85f29b643aba990800254a4a5a9 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:27:01Z |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-7e27a85f29b643aba990800254a4a5a92024-04-16T21:32:05ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-01-017364376Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axisYaru Guo0Feng Mei1Ying Huang2Siqin Ma3Yan Wei4Xuehui Zhang5Mingming Xu6Ying He7Boon Chin Heng8Lili Chen9Xuliang Deng10Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, ChinaDepartment of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, PR China; Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, PR ChinaDepartment of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaCentral Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, PR ChinaDepartment of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China; Corresponding author. Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, China; Department of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, PR China; Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China; Corresponding author. Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, China.Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this study, we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues. Stiffened matrix promoted sprouting from endothelial cell (EC) spheroids and upregulated expressions of tip cell-enriched genes in vitro. Moreover, tip cells showed increased cellular stiffness, more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs. We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state. YAP is subsequently activated and translocated into nucleus, leading to increased tip cell specification. p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification. Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis, shedding light on the role of mechanotransduction in tip cell formation. This is of special significance in biomaterial design and treatment of some pathological situations.http://www.sciencedirect.com/science/article/pii/S2452199X2100253XTip cellsMechanotransductionStiffnessAngiogenesisExtracellular matrix |
| spellingShingle | Yaru Guo Feng Mei Ying Huang Siqin Ma Yan Wei Xuehui Zhang Mingming Xu Ying He Boon Chin Heng Lili Chen Xuliang Deng Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis Bioactive Materials Tip cells Mechanotransduction Stiffness Angiogenesis Extracellular matrix |
| title | Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis |
| title_full | Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis |
| title_fullStr | Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis |
| title_full_unstemmed | Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis |
| title_short | Matrix stiffness modulates tip cell formation through the p-PXN-Rac1-YAP signaling axis |
| title_sort | matrix stiffness modulates tip cell formation through the p pxn rac1 yap signaling axis |
| topic | Tip cells Mechanotransduction Stiffness Angiogenesis Extracellular matrix |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X2100253X |
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