PDGF-D-induced immunoproteasome activation and cell-cell interactions
Platelet-derived growth factor-D (PDGF-D) is abundantly expressed in ocular diseases. Yet, it remains unknown whether and how PDGF-D affects ocular cells or cell-cell interactions in the eye. In this study, using single-cell RNA sequencing (scRNA-seq) and a mouse model of PDGF-D overexpression in re...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023001460 |
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| author | Jianing Zhang Wanhong Li Zhen Xiong Juanhua Zhu Xiangrong Ren Shasha Wang Haiqing Kuang Xianchai Lin Antonio Mora Xuri Li |
| author_facet | Jianing Zhang Wanhong Li Zhen Xiong Juanhua Zhu Xiangrong Ren Shasha Wang Haiqing Kuang Xianchai Lin Antonio Mora Xuri Li |
| author_sort | Jianing Zhang |
| collection | DOAJ |
| description | Platelet-derived growth factor-D (PDGF-D) is abundantly expressed in ocular diseases. Yet, it remains unknown whether and how PDGF-D affects ocular cells or cell-cell interactions in the eye. In this study, using single-cell RNA sequencing (scRNA-seq) and a mouse model of PDGF-D overexpression in retinal pigment epithelial (RPE) cells, we found that PDGF-D overexpression markedly upregulated the key immunoproteasome genes, leading to increased antigen processing/presentation capacity of RPE cells. Also, more than 6.5-fold ligand-receptor pairs were found in the PDGF-D overexpressing RPE-choroid tissues, suggesting markedly increased cell-cell interactions. Moreover, in the PDGF-D-overexpressing tissues, a unique cell population with a transcriptomic profile of both stromal cells and antigen-presenting RPE cells was detected, suggesting PDGF-D-induced epithelial-mesenchymal transition of RPE cells. Importantly, administration of ONX-0914, an immunoproteasome inhibitor, suppressed choroidal neovascularization (CNV) in a mouse CNV model in vivo. Together, we show that overexpression of PDGF-D increased pro-angiogenic immunoproteasome activities, and inhibiting immunoproteasome pathway may have therapeutic value for the treatment of neovascular diseases. |
| first_indexed | 2024-03-08T21:31:00Z |
| format | Article |
| id | doaj.art-46518d7c96e24950bb4b4761b5dc1970 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T21:31:00Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-46518d7c96e24950bb4b4761b5dc19702023-12-21T07:31:21ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012124052418PDGF-D-induced immunoproteasome activation and cell-cell interactionsJianing Zhang0Wanhong Li1Zhen Xiong2Juanhua Zhu3Xiangrong Ren4Shasha Wang5Haiqing Kuang6Xianchai Lin7Antonio Mora8Xuri Li9State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, China; Corresponding authors.Joint School of Life Sciences, Guangzhou Medical University and Guangzhou Institutes of Biomedicine and Health (Chinese Academy of Sciences), Xinzao, Panyu district, Guangzhou 511436, Guangdong, China; Corresponding authors.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, China; Corresponding authors.Platelet-derived growth factor-D (PDGF-D) is abundantly expressed in ocular diseases. Yet, it remains unknown whether and how PDGF-D affects ocular cells or cell-cell interactions in the eye. In this study, using single-cell RNA sequencing (scRNA-seq) and a mouse model of PDGF-D overexpression in retinal pigment epithelial (RPE) cells, we found that PDGF-D overexpression markedly upregulated the key immunoproteasome genes, leading to increased antigen processing/presentation capacity of RPE cells. Also, more than 6.5-fold ligand-receptor pairs were found in the PDGF-D overexpressing RPE-choroid tissues, suggesting markedly increased cell-cell interactions. Moreover, in the PDGF-D-overexpressing tissues, a unique cell population with a transcriptomic profile of both stromal cells and antigen-presenting RPE cells was detected, suggesting PDGF-D-induced epithelial-mesenchymal transition of RPE cells. Importantly, administration of ONX-0914, an immunoproteasome inhibitor, suppressed choroidal neovascularization (CNV) in a mouse CNV model in vivo. Together, we show that overexpression of PDGF-D increased pro-angiogenic immunoproteasome activities, and inhibiting immunoproteasome pathway may have therapeutic value for the treatment of neovascular diseases.http://www.sciencedirect.com/science/article/pii/S2001037023001460Single-cell RNA sequencingPDGF-DImmunoproteasomeCell-cell interactionImmune cell infiltration |
| spellingShingle | Jianing Zhang Wanhong Li Zhen Xiong Juanhua Zhu Xiangrong Ren Shasha Wang Haiqing Kuang Xianchai Lin Antonio Mora Xuri Li PDGF-D-induced immunoproteasome activation and cell-cell interactions Computational and Structural Biotechnology Journal Single-cell RNA sequencing PDGF-D Immunoproteasome Cell-cell interaction Immune cell infiltration |
| title | PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| title_full | PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| title_fullStr | PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| title_full_unstemmed | PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| title_short | PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| title_sort | pdgf d induced immunoproteasome activation and cell cell interactions |
| topic | Single-cell RNA sequencing PDGF-D Immunoproteasome Cell-cell interaction Immune cell infiltration |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023001460 |
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