Bibliographic Details
| Title: |
PDGF-D-induced immunoproteasome activation and cell-cell interactions |
| Authors: |
Jianing Zhang, Wanhong Li, Zhen Xiong, Juanhua Zhu, Xiangrong Ren, Shasha Wang, Haiqing Kuang, Xianchai Lin, Antonio Mora, Xuri Li |
| Source: |
Computational and Structural Biotechnology Journal, Vol 21, Iss , Pp 2405-2418 (2023) |
| Publisher Information: |
Elsevier, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Biotechnology |
| Subject Terms: |
Single-cell RNA sequencing, PDGF-D, Immunoproteasome, Cell-cell interaction, Immune cell infiltration, Biotechnology, TP248.13-248.65 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2001-0370 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2001037023001460; https://doaj.org/toc/2001-0370 |
| DOI: |
10.1016/j.csbj.2023.03.047 |
| Access URL: |
https://doaj.org/article/46518d7c96e24950bb4b4761b5dc1970 |
| Accession Number: |
edsdoj.46518d7c96e24950bb4b4761b5dc1970 |
| Database: |
Directory of Open Access Journals |
