Effects of tumor necrosis factor-α inhibition on kidney fibrosis and inflammation in a mouse model of aristolochic acid nephropathy.

Albuminuria / drug therapy Animals Aristolochic Acids / pharmacology Collagen / metabolism Disease Models, Animal Etanercept / pharmacology Fibrosis / drug therapy Inflammation / drug therapy Interleukin-1beta / metabolism Interleukin-6 / metabolism Kidney / drug effects Male Mice Mice, Inbred C57BL RNA, Messenger / metabolism Renal Insufficiency, Chronic / chemically induced Tumor Necrosis Factor-alpha / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 12 2021
Historique:
received: 17 09 2021
accepted: 22 11 2021
entrez: 9 12 2021
pubmed: 10 12 2021
medline: 28 1 2022
Statut: epublish

Résumé

Tumor necrosis factor (TNF)-α is a potent mediator of inflammation and is involved in the pathophysiology of chronic kidney disease (CKD). However, the effects of TNF-α inhibition on the progression of kidney fibrosis have not been fully elucidated. We examined the effects of TNF-α inhibition by etanercept (ETN) on kidney inflammation and fibrosis in mice with aristolochic acid (AA) nephropathy as a model of kidney fibrosis. C57BL/6 J mice were administered AA for 4 weeks, followed by a 4-week remodeling period. The mice exhibited kidney fibrosis, functional decline, and albuminuria concomitant with increases in renal mRNA expression of inflammation- and fibrosis-related genes. The 8-week ETN treatment partially but significantly attenuated kidney fibrosis and ameliorated albuminuria without affecting kidney function. These findings were accompanied by significant suppression of interleukin (IL)-1β, IL-6, and collagen types I and III mRNA expression. Moreover, ETN tended to reduce the AA-induced increase in interstitial TUNEL-positive cells with a significant reduction in Bax mRNA expression. Renal phosphorylated p38 MAPK was significantly upregulated by AA but was normalized by ETN. These findings indicate a substantial role for the TNF-α pathway in the pathogenesis of kidney fibrosis and suggest that TNF-α inhibition could become an adjunct therapeutic strategy for CKD with fibrosis.

Identifiants

DOI: 10.1038/s41598-021-02864-1 PMID: 34880315 PMC: PMC8654826
pubmed: 34880315
doi: 10.1038/s41598-021-02864-1
pii: 10.1038/s41598-021-02864-1
pmc: PMC8654826
doi:

Substances chimiques

Aristolochic Acids 0
Interleukin-1beta 0
Interleukin-6 0
RNA, Messenger 0
Tumor Necrosis Factor-alpha 0
Collagen 9007-34-5
aristolochic acid I 94218WFP5T
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24
Etanercept OP401G7OJC

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

23587

Informations de copyright

© 2021. The Author(s).

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Auteurs

Shinya Taguchi (S)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Kengo Azushima (K)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan. azushima@yokohama-cu.ac.jp.

Takahiro Yamaji (T)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.

Shingo Urate (S)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Toru Suzuki (T)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Eriko Abe (E)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Shohei Tanaka (S)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Shunichiro Tsukamoto (S)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Daisuke Kamimura (D)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Sho Kinguchi (S)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

Akio Yamashita (A)

Department of Investigative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Hiromichi Wakui (H)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan. hiro1234@yokohama-cu.ac.jp.

Kouichi Tamura (K)

Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan.

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations urologiques › Protéinurie › Albuminurie › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Composés polycycliques › Hydrocarbures aromatiques polycycliques › Phénanthrènes › Acides aristolochiques › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux facteurs de nécrose tumorale › Étanercept › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Monokines › Interleukine-1 › Interleukine-1 bêta › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-6 › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Effects of tumor necrosis factor-α inhibition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Effects of tumor necrosis factor-α inhibition...