Knockout of Bruton's tyrosine kinase in macrophages attenuates diabetic nephropathy in streptozotocin-induced mice
AJTR Copyright © 2021..
As a cytoplasmic tyrosine kinase in the Tec family, Bruton's tyrosine kinase (Btk) participates in various biological processes, including cell growth, differentiation, and apoptosis. Although recent studies have indicated that Btk is involved in pro-inflammatory cytokine production, the underlying impact of Btk on the development and pathogenesis of diabetic nephropathy (DN) has not been elucidated. The aim of this study was to determine whether Btk knockout (KO) could reduce inflammation and kidney injury in DN. First, diabetic mice models were established via an intraperitoneal injection of streptozotocin. Thereafter, the underlying mechanism was explored by comparing Btk flox/flox Lyz-Cre mice to wild-type (C57BL/6N) mice. Albuminuria was significantly reduced, and kidney injuries were attenuated in Btk conditional deletion diabetic mice. More importantly, these changes were demonstrated to be associated with decreased levels of pro-inflammatory cytokines owing to the downregulation of the MAPK and NF-κB signaling pathways. Collectively, these findings indicate that Btk plays a critical role in the regulation of kidney inflammation and provides a prospective therapeutic strategy for the treatment of DN.
Medienart: |
Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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Enthalten in: |
American journal of translational research - 13(2021), 11 vom: 22., Seite 12352-12363 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Fan, Zhe [VerfasserIn] |
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Themen: |
Bruton’s tyrosine kinases |
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Anmerkungen: |
Date Revised 28.12.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM334923468 |
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520 | |a AJTR Copyright © 2021. | ||
520 | |a As a cytoplasmic tyrosine kinase in the Tec family, Bruton's tyrosine kinase (Btk) participates in various biological processes, including cell growth, differentiation, and apoptosis. Although recent studies have indicated that Btk is involved in pro-inflammatory cytokine production, the underlying impact of Btk on the development and pathogenesis of diabetic nephropathy (DN) has not been elucidated. The aim of this study was to determine whether Btk knockout (KO) could reduce inflammation and kidney injury in DN. First, diabetic mice models were established via an intraperitoneal injection of streptozotocin. Thereafter, the underlying mechanism was explored by comparing Btk flox/flox Lyz-Cre mice to wild-type (C57BL/6N) mice. Albuminuria was significantly reduced, and kidney injuries were attenuated in Btk conditional deletion diabetic mice. More importantly, these changes were demonstrated to be associated with decreased levels of pro-inflammatory cytokines owing to the downregulation of the MAPK and NF-κB signaling pathways. Collectively, these findings indicate that Btk plays a critical role in the regulation of kidney inflammation and provides a prospective therapeutic strategy for the treatment of DN | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Bruton’s tyrosine kinases | |
650 | 4 | |a Diabetic nephropathy | |
650 | 4 | |a inflammation | |
650 | 4 | |a macrophage | |
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700 | 1 | |a Xia, Lingling |e verfasserin |4 aut | |
700 | 1 | |a Wu, Yonggui |e verfasserin |4 aut | |
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