Inhibition of RAC attenuates Adriamycin-induced podocyte injury
Copyright © 2024 Nanjing medical university affliated children's hospital. Published by Elsevier Inc. All rights reserved..
Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS). To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:709 |
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| Enthalten in: |
Biochemical and biophysical research communications - 709(2024) vom: 21. Apr., Seite 149807 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Hao [VerfasserIn] |
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| Links: |
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| Themen: |
80168379AG |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2024.149807 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370420799 |
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| 520 | |a Copyright © 2024 Nanjing medical university affliated children's hospital. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS). To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Bioinformatic analysis | |
| 650 | 4 | |a Molecule inhibitor EHT-1864 | |
| 650 | 4 | |a Podocyte injury | |
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| 700 | 1 | |a Huang, Songming |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Guixia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Aihua |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jing |e verfasserin |4 aut | |
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