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LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4.

Liu, Y ; Zhang, M ; et al.
In: Acta diabetologica, Jg. 60 (2023-04-01), Heft 4, S. 563-577
Online academicJournal
Zugriff:
View record at Springer (Volltext)

Aims: LncRNA SNHG16 and Toll-like receptor-4 (TLR4) participate in diabetes nephropathy. This study investigated whether SNHG16 regulates diabetic renal injury (DRI) via TLR4 and its related mechanism.

Methods: Diabetic mice and high glucose (HG)-induced HRMCs were used to examine the expressions of SNHG16 and TLR4. The SNHG16 expression, cytokines, reactive oxygen species, MDA, SOD, GSH, and fibrosis-related proteins were evaluated in HG-induced HRMCs transfected with sh-NC or sh-SHNG16. RNA immunoprecipitation and RNA pull-down determined the interaction between SNHG16 and EIF4A3 or TLR4 and EIF4A3. We used HG-treated HRMCs or diabetic mice to investigate the roles of TLR4 or SNHG16 in renal injuries.

Results: Both SNHG16 and TLR4 were upregulated in diabetic conditions. HG increased serum Scr and BUN, led to significant fibrosis, increased inflammation- and renal fibrosis-related proteins in mice, and increased ROS, MDA, and decreased SOD and GSH in HRMCs. SNHG16 silencing diminished HG-upregulated SNHG16, decreased HG-increased cytokines secretion, ROS, MDA, and fibrosis but increased SOD and GSH. RIP and RNA pull-down confirmed that SNHG16 recruits EIF4A3 to stabilize TLR4 mRNA. TLR4 knockdown alleviated HG-induced renal injuries by suppressing RAS and NF-κB-mediated activation of NLRP3 inflammasomes. SNHG16 knockdown alleviated HG-induced renal injuries in HG-induced HRMCs or diabetic mice. Interestingly, TLR4 overexpression reversed the effects of SNHG16 knockdown. Mechanistically, SNHG16 knockdown alleviated HG-induced renal injuries by suppressing TLR4.

Conclusion: SNHG16 accelerated HG-induced renal injuries via recruiting EIF4A3 to enhance the stabilization of TLR4 mRNA. The SNGHG16/ELF4A3/TLR4 axis might be a novel target for treating DRI.

(© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Titel:
LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4.
Autor/in / Beteiligte Person: Liu, Y ; Zhang, M ; Zhong, H ; Xie, N ; Wang, Y ; Ding, S ; Su, X
Link:
Zeitschrift: Acta diabetologica, Jg. 60 (2023-04-01), Heft 4, S. 563-577
Veröffentlichung: Berlin : Springer Verlag ; <i>Original Publication</i>: Berlin : Springer International, c1991-, 2023
Medientyp: academicJournal
ISSN: 1432-5233 (electronic)
DOI: 10.1007/s00592-022-02021-8
Schlagwort:
  • Animals
  • Mice
  • Cytokines
  • Fibrosis
  • Inflammasomes metabolism
  • Inflammation metabolism
  • NF-kappa B metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein metabolism
  • Reactive Oxygen Species metabolism
  • RNA, Messenger
  • Superoxide Dismutase
  • Toll-Like Receptor 4 genetics
  • Humans
  • Diabetes Mellitus, Experimental genetics
  • Diabetes Mellitus, Experimental metabolism
  • Diabetic Nephropathies genetics
  • Diabetic Nephropathies metabolism
  • RNA, Long Noncoding genetics
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article
  • Language: English
  • [Acta Diabetol] 2023 Apr; Vol. 60 (4), pp. 563-577. <i>Date of Electronic Publication: </i>2023 Jan 20.
  • MeSH Terms: Diabetes Mellitus, Experimental* / genetics ; Diabetes Mellitus, Experimental* / metabolism ; Diabetic Nephropathies* / genetics ; Diabetic Nephropathies* / metabolism ; RNA, Long Noncoding* / genetics ; Animals ; Mice ; Cytokines ; Fibrosis ; Inflammasomes / metabolism ; Inflammation / metabolism ; NF-kappa B / metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein / genetics ; NLR Family, Pyrin Domain-Containing 3 Protein / metabolism ; Reactive Oxygen Species / metabolism ; RNA, Messenger ; Superoxide Dismutase ; Toll-Like Receptor 4 / genetics ; Humans
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  • Grant Information: 2020A1515110130 Guangdong Provincial Basic and Applied Basic Research Fund Regional Joint Fund Project (Youth Fund Project)
  • Contributed Indexing: Keywords: Diabetic nephropathy; High glucose; LncRNA SNHG16; NRLP3 inflammasome; RAS; TLR4
  • Substance Nomenclature: 0 (Cytokines) ; 0 (Inflammasomes) ; 0 (NF-kappa B) ; 0 (NLR Family, Pyrin Domain-Containing 3 Protein) ; 0 (Nlrp3 protein, mouse) ; 0 (Reactive Oxygen Species) ; 0 (RNA, Long Noncoding) ; 0 (RNA, Messenger) ; EC 1.15.1.1 (Superoxide Dismutase) ; 0 (Tlr4 protein, mouse) ; 0 (Toll-Like Receptor 4) ; 0 (SNHG16 lncRNA, human) ; 0 (TLR4 protein, human) ; 0 (NLRP3 protein, human)
  • Entry Date(s): Date Created: 20230119 Date Completed: 20230331 Latest Revision: 20230331
  • Update Code: 20240513

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