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Telomere dysfunctio...
Telomere dysfunction promotes small vessel vasculitis via the LL37-NETs-dependent mechanism
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- Lu, Yingying (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Jiang, Hong (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Li, Bingjue (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Cao, Luxi (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Shen, Qixia (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Yi, Weiwei (författare)
- Hangzhou Normal Univ, Peoples R China
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- Ju, Zhenyu (författare)
- Hangzhou Normal Univ, Peoples R China
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- Chen, Liangliang (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Han, Fei (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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- Appelgren, Daniel (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten
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- Segelmark, Mårten, 1957- (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Njurmedicinska kliniken US
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- de Buhr, Nicole (författare)
- Univ Vet Med Hannover, Germany
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- von Koeckritz-Blickwede, Maren (författare)
- Univ Vet Med Hannover, Germany
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- Chen, Jianghua (författare)
- Zhejiang Univ, Peoples R China; State Adm Tradit Chinese Med PR China, Peoples R China; Minist Hlth, Peoples R China; Key Lab Nephropathy, Peoples R China
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(creator_code:org_t)
- AME PUBL CO, 2020
- 2020
- Engelska.
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Ingår i: Annals of Translational Medicine. - : AME PUBL CO. - 2305-5839 .- 2305-5847. ; 8:6
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://atm.amegroup...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- Background: Small vessel vasculitis (SVV) is a group of systemic autoimmune diseases that are mediated by neutrophil extracellular traps (NETs) in response to cathelicidin LL37, an aging molecular marker, which could be induced by telomere dysfunction. Therefore, in this study, we evaluated the hypothesis that telomere dysfunction in neutrophils may promote SVV via an LL37-NETs-dependent mechanism. Methods: We contrasted the release of neutrophil NETs from mice with telomere dysfunction, mice with DNA damage and wide-type mice. Neutrophil telomere length, the expression of LL37, and the formation of NETs were measured in SVV patients and healthy controls (HCs). The co-expression of gamma H2AX, LL37, and NETs were detected in SVV patients to evaluate the association of the immune aging of neutrophils and pro-inflammatory conditions. LL37 inhibitor was used to verify its key role in NETs release in SVV patients and DNA damage mice. Results: We found that NETs were over-induced by telomere dysfunction and DNA damage in mice, which may be associated with a marked increase in LL37. For patients with SVV, telomeres in neutrophils were significantly shortened, which was also associated with higher levels of LL37 and NETs. Inhibition of LL37 reduced the NETs released from neutrophils. Conclusions: Taken together, the results of these studies suggest that dysfunction of telomeres may promote SVV through the mechanism of LL37-dependent NETs. Thus, targeting the LL37-NETs may be a novel therapy for SVV.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Telomere dysfunction; DNA damage; small vessel vasculitis (SVV); LL37; neutrophil extracellular traps (NETs)
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- ref (ämneskategori)
- art (ämneskategori)
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Lu, Yingying
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Jiang, Hong
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Li, Bingjue
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Cao, Luxi
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Shen, Qixia
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Yi, Weiwei
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visa fler...
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Ju, Zhenyu
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Chen, Liangliang
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Han, Fei
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Appelgren, Danie ...
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Segelmark, Mårte ...
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de Buhr, Nicole
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von Koeckritz-Bl ...
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Chen, Jianghua
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Linköpings universitet