Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis
© 2024. The Author(s)..
BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear.
METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis.
RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation.
CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Cell communication and signaling : CCS - 22(2024), 1 vom: 09. Apr., Seite 223 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhu, Yufeng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Acute kidney injury |
|---|
| Anmerkungen: |
Date Completed 11.04.2024 Date Revised 24.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12964-024-01600-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370840674 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370840674 | ||
| 003 | DE-627 | ||
| 005 | 20240424232152.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240410s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12964-024-01600-2 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1385.xml |
| 035 | |a (DE-627)NLM370840674 | ||
| 035 | |a (NLM)38594728 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhu, Yufeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis |
| 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 11.04.2024 | ||
| 500 | |a Date Revised 24.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear | ||
| 520 | |a METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis | ||
| 520 | |a RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation | ||
| 520 | |a CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute kidney injury | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Autophagy-related 5 | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a Renal fibrosis | |
| 650 | 7 | |a Atg5 protein, mouse |2 NLM | |
| 650 | 7 | |a Autophagy-Related Protein 5 |2 NLM | |
| 650 | 7 | |a CCR6 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, CCR6 |2 NLM | |
| 650 | 7 | |a CCL20 protein, mouse |2 NLM | |
| 700 | 1 | |a Tan, Jiexing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuanzhan |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaoyong |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Ziguo |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Huifang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhiming |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xiaotao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Li |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell communication and signaling : CCS |d 2003 |g 22(2024), 1 vom: 09. Apr., Seite 223 |w (DE-627)NLM143253794 |x 1478-811X |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:1 |g day:09 |g month:04 |g pages:223 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12964-024-01600-2 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 1 |b 09 |c 04 |h 223 | ||