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Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan
Nature communications, 2019-04, Vol.10 (1), p.1476-1476, Article 1476
2019
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Autor(en) / Beteiligte
Titel
Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan
Ist Teil von
  • Nature communications, 2019-04, Vol.10 (1), p.1476-1476, Article 1476
Ort / Verlag
London: Nature Publishing Group UK
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
  • Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants including patients with stage 1–5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD. Accurate monitoring of chronic kidney disease (CKD) progression is essential for efficient disease management. Here Chen et al. identify five serum metabolites in patients with stage 1–5 CKD whose levels associate with disease progression, and find that 5-methoxytryptophan and its regulatory enzyme TPH-1 exert anti-fibrotic effects in mouse models of kidney injury.
Sprache
Englisch
Identifikatoren
ISSN: 2041-1723
eISSN: 2041-1723
DOI: 10.1038/s41467-019-09329-0
Titel-ID: cdi_doaj_primary_oai_doaj_org_article_4a04997a433f49e4a807e4cf744638af
Format
–
Schlagworte
13/51, 13/89, 14/19, 38, 38/47, 631/45/320, 64/60, 692/4022/1585/104, 82/58, 82/80, Acetylcarnitine - metabolism, Animals, Canavanine - analogs & derivatives, Canavanine - metabolism, Carnitine - analogs & derivatives, Carnitine - metabolism, Case-Control Studies, Disease Models, Animal, Disease Progression, End-stage renal disease, Fibrosis, Fibrosis - metabolism, Gene Knock-In Techniques, Gene Knockdown Techniques, Humanities and Social Sciences, Humans, I-kappa B Proteins - metabolism, Inflammation - metabolism, Injury prevention, Ischemia, Kelch-Like ECH-Associated Protein 1 - metabolism, Kidney - cytology, Kidney - drug effects, Kidney - pathology, Kidney diseases, Kidneys, Metabolites, Metabolomics, Mice, multidisciplinary, NF-E2-Related Factor 2 - metabolism, NF-kappa B - metabolism, NF-κB protein, Renal Insufficiency, Chronic - metabolism, Reperfusion, Science, Science (multidisciplinary), Severity of Illness Index, Signal Transduction, Signaling, Taurine - metabolism, Tryptophan, Tryptophan - analogs & derivatives, Tryptophan - metabolism, Tryptophan - pharmacology, Tryptophan hydroxylase, Tryptophan Hydroxylase - genetics, Ureteral Obstruction

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