UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation
As a hallmark of skin aging, senescent human dermal fibroblasts (HDFs) are known to lose the ability to divide. However, they can still interact with their cellular environment and the surrounding matrix. As the skin ages, the progressive slowing down of HDFs function decreases the skin's struc...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/164055 |
| _version_ | 1811691925525233664 |
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| author | Yao, Xuefeng Li, Huaqiong Chen, Liping Tan, Lay Poh |
| author2 | School of Materials Science and Engineering |
| author_facet | School of Materials Science and Engineering Yao, Xuefeng Li, Huaqiong Chen, Liping Tan, Lay Poh |
| author_sort | Yao, Xuefeng |
| collection | NTU |
| description | As a hallmark of skin aging, senescent human dermal fibroblasts (HDFs) are known to lose the ability to divide. However, they can still interact with their cellular environment and the surrounding matrix. As the skin ages, the progressive slowing down of HDFs function decreases the skin's structural integrity, which is more serious than if there is the dermal collagen matrix eroded. This leads to matters of the unbalanced barrier under the skin, skin fragility, inadequate wound healing, as well as other cosmetic issues. It is also well documented that skin aging comes with significant stiffness increases. Therefore, understanding the interactions between HDFs and the surrounding microenvironments during senescence may provide insights into skin aging. Here we aim to investigate matrix stiffness' effect on HDF senescence and elucidate possible mechanisms that make HDFs senescent. In our experiments, HDFs were cultivated on Polydimethylsiloxane (PDMS) with various stiffnesses and exposed to UV light to trigger senescence. Results show that HDFs are significantly affected by senescence when cultured on a matrix with stiffness. However, the cells are not significantly affected when cultured on a low stiffness matrix. The following characterization revealed cells cultured on stiff substrates under UV exposure had stimulated the nucleus factor kappa-B (NF-κB) activation. In contrast, cells on a matrix of softness only displayed low activation of NF-κB. NF-κB activity suppression with ammonium pyrrolidine dithiocarbamate (PDTC) decreases UV-induced HDFs senescence on stiff substrates. Taken together, we demonstrated that soft matrix defends HDFs against ultraviolet-induced senescence by inhibiting the activation of NF-κB. |
| first_indexed | 2024-10-01T06:27:38Z |
| format | Journal Article |
| id | ntu-10356/164055 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:27:38Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1640552023-07-14T16:07:06Z UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation Yao, Xuefeng Li, Huaqiong Chen, Liping Tan, Lay Poh School of Materials Science and Engineering Engineering::Materials Human Dermal Fibroblasts Matrix Stiffness As a hallmark of skin aging, senescent human dermal fibroblasts (HDFs) are known to lose the ability to divide. However, they can still interact with their cellular environment and the surrounding matrix. As the skin ages, the progressive slowing down of HDFs function decreases the skin's structural integrity, which is more serious than if there is the dermal collagen matrix eroded. This leads to matters of the unbalanced barrier under the skin, skin fragility, inadequate wound healing, as well as other cosmetic issues. It is also well documented that skin aging comes with significant stiffness increases. Therefore, understanding the interactions between HDFs and the surrounding microenvironments during senescence may provide insights into skin aging. Here we aim to investigate matrix stiffness' effect on HDF senescence and elucidate possible mechanisms that make HDFs senescent. In our experiments, HDFs were cultivated on Polydimethylsiloxane (PDMS) with various stiffnesses and exposed to UV light to trigger senescence. Results show that HDFs are significantly affected by senescence when cultured on a matrix with stiffness. However, the cells are not significantly affected when cultured on a low stiffness matrix. The following characterization revealed cells cultured on stiff substrates under UV exposure had stimulated the nucleus factor kappa-B (NF-κB) activation. In contrast, cells on a matrix of softness only displayed low activation of NF-κB. NF-κB activity suppression with ammonium pyrrolidine dithiocarbamate (PDTC) decreases UV-induced HDFs senescence on stiff substrates. Taken together, we demonstrated that soft matrix defends HDFs against ultraviolet-induced senescence by inhibiting the activation of NF-κB. Nanyang Technological University The authors acknowledged the financial support from Nanyang Technological University, Singapore for PhD scholarship and funding; Zhejiang Provincial Natural Science Foundation (LY20C070010), and start-up funding from Wenzhou Institute, University of Chinese Academy of Sciences (WIUCASQD2019002). 2023-01-03T08:32:54Z 2023-01-03T08:32:54Z 2022 Journal Article Yao, X., Li, H., Chen, L. & Tan, L. P. (2022). UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation. Engineered Regeneration, 3(4), 365-373. https://dx.doi.org/10.1016/j.engreg.2022.08.002 2666-1381 https://hdl.handle.net/10356/164055 10.1016/j.engreg.2022.08.002 2-s2.0-85136133248 4 3 365 373 en Engineered Regeneration application/pdf |
| spellingShingle | Engineering::Materials Human Dermal Fibroblasts Matrix Stiffness Yao, Xuefeng Li, Huaqiong Chen, Liping Tan, Lay Poh UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title | UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title_full | UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title_fullStr | UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title_full_unstemmed | UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title_short | UV-induced senescence of human dermal fibroblasts restrained by low-stiffness matrix by inhibiting NF-κB activation |
| title_sort | uv induced senescence of human dermal fibroblasts restrained by low stiffness matrix by inhibiting nf κb activation |
| topic | Engineering::Materials Human Dermal Fibroblasts Matrix Stiffness |
| url | https://hdl.handle.net/10356/164055 |
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