Inhibition of TLR4/NF-κB pathway and endoplasmic reticulum stress by overexpressed S100A4 ameliorates retinal ischemia-reperfusion injury of mice
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
Retinal ischemia exists in various ischemic retinopathies including glaucoma, contributing to the death of retinal neurons. Calcium binding protein S100A4 is important in tumors, and our previous study found that S100A4 protects retinal ganglion cells (RGCs) against retinal ischemia-reperfusion (I/R) injury. This study was aimed to further discuss the neuroprotection and mechanisms of S100A4 in retinal I/R of mice. The rAAV-EF1α-s100a4-EGFP-WPRE or rAAV-EF1α-EGFP-WPRE-Pa was injected intravitreally 4 weeks before I/R. S100A4, molecules in TLR4 signaling pathway and endoplasmic reticulum (ER) stress branches, inflammatory molecules, and surviving RGCs and cholinergic amacrine (ChAT) cells were determined by quantitative PCR, western blot, or immunofluorescent staining. The apoptosis and necrosis of retinal neurons induced by I/R were inhibited by overexpressed S100A4. RGCs, ChAT cells, and the retinal function were preserved by S100A4 overexpressing 7 days after I/R. Mechanistically, the beneficial effects of S100A4 may be mediated by inhibiting the activation of TLR4 signaling pathway and alleviating ER stress, leading to the attenuation of inflammatory response of the retina after I/R. Our findings indicated that S100A4 has neuroprotective effect against retinal I/R injury, and promoting S100A4 expression may be an effective strategy to inhibit retinal neurons from degeneration in ischemic retinopathy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
|---|---|
| Enthalten in: |
Molecular neurobiology - 61(2024), 4 vom: 09. Apr., Seite 2228-2240 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yang, Jiayi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ER stress |
|---|
| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12035-023-03709-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36364640X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36364640X | ||
| 003 | DE-627 | ||
| 005 | 20240401232358.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12035-023-03709-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1359.xml |
| 035 | |a (DE-627)NLM36364640X | ||
| 035 | |a (NLM)37872355 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yang, Jiayi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition of TLR4/NF-κB pathway and endoplasmic reticulum stress by overexpressed S100A4 ameliorates retinal ischemia-reperfusion injury of mice |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.03.2024 | ||
| 500 | |a Date Revised 01.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. | ||
| 520 | |a Retinal ischemia exists in various ischemic retinopathies including glaucoma, contributing to the death of retinal neurons. Calcium binding protein S100A4 is important in tumors, and our previous study found that S100A4 protects retinal ganglion cells (RGCs) against retinal ischemia-reperfusion (I/R) injury. This study was aimed to further discuss the neuroprotection and mechanisms of S100A4 in retinal I/R of mice. The rAAV-EF1α-s100a4-EGFP-WPRE or rAAV-EF1α-EGFP-WPRE-Pa was injected intravitreally 4 weeks before I/R. S100A4, molecules in TLR4 signaling pathway and endoplasmic reticulum (ER) stress branches, inflammatory molecules, and surviving RGCs and cholinergic amacrine (ChAT) cells were determined by quantitative PCR, western blot, or immunofluorescent staining. The apoptosis and necrosis of retinal neurons induced by I/R were inhibited by overexpressed S100A4. RGCs, ChAT cells, and the retinal function were preserved by S100A4 overexpressing 7 days after I/R. Mechanistically, the beneficial effects of S100A4 may be mediated by inhibiting the activation of TLR4 signaling pathway and alleviating ER stress, leading to the attenuation of inflammatory response of the retina after I/R. Our findings indicated that S100A4 has neuroprotective effect against retinal I/R injury, and promoting S100A4 expression may be an effective strategy to inhibit retinal neurons from degeneration in ischemic retinopathy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ER stress | |
| 650 | 4 | |a Ischemia-reperfusion | |
| 650 | 4 | |a Neuroprotection | |
| 650 | 4 | |a S100A4 | |
| 650 | 4 | |a TLR4 signaling pathway | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Toll-Like Receptor 4 |2 NLM | |
| 650 | 7 | |a S100a4 protein, mouse |2 NLM | |
| 700 | 1 | |a Zhang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jinyuan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Yiqiao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular neurobiology |d 1990 |g 61(2024), 4 vom: 09. Apr., Seite 2228-2240 |w (DE-627)NLM012626961 |x 1559-1182 |7 nnns |
| 773 | 1 | 8 | |g volume:61 |g year:2024 |g number:4 |g day:09 |g month:04 |g pages:2228-2240 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12035-023-03709-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 61 |j 2024 |e 4 |b 09 |c 04 |h 2228-2240 | ||