Role of the CTRP6/AMPK pathway in kidney fibrosis through the promotion of fatty acid oxidation

Nov 27, 2020European journal of pharmacology

How the CTRP6/AMPK pathway may reduce kidney scarring by increasing fat breakdown

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

CTRP6 is associated with decreased levels of p-AMPK in kidney fibrosis.

CTRP6 and the enzymes involved in fatty acid oxidation (FAO) were tested in both live animals and cell cultures.
A reduction in CTRP6 and p-AMPK was observed in kidney fibrosis induced by urinary obstruction and in kidney cells treated with TGF-β1.
Defective FAO was noted during the progression of kidney fibrosis.
Exogenous recombinant CTRP6 inhibited extracellular matrix deposition and promoted AMPK phosphorylation by enhancing FAO.
The protective effects of CTRP6 on FAO and TGF-β1-induced extracellular matrix deposition were reversed by compound C, an AMPK inhibitor.
The mediation of FAO by CTRP6 may play a key role in kidney fibrosis through its effects on renal tubular epithelial cell differentiation.

AI simplified

CTRP6, a newly identified adiponectin analogue, has been shown to be involved in inflammation, diabetes and cardiovascular diseases. Recently, increasing evidence has shown that CTRP6 plays a critical role in fibrotic diseases, such as myocardial fibrosis and skin fibrosis. FAO, an important energy source for kidney proximal tubular cells, also participates in the process of fibrosis. Therefore, our study aimed to investigate the effect of CTRP6 on mediating FAO in kidney fibrosis and the underlying associated mechanism. Firstly, the activity of CTRP6 and the key enzymes of FAO (CPT1A, ACOX1) were tested in vivo and vitro. Next, the regulatory effect of CTRP6/AMPK on FAO was accessed in animal models and in cell lines. Additionally, we explored the effect of exogenous recombinant CTRP6 on renal tubular epithelial cell differentiation. Decreased CTRP6 and p-AMPK were detected in UUO-induced kidney fibrosis and in TGF-β1-treated HK-2 cells. We also observed that defective FAO occurred during kidney fibrosis. Moreover, the human CTRP6 peptide could inhibit the ECM deposition and promote the phosphorylation of AMPK by promoting FAO. However, the inhibitory effects of CTRP6 on TGF-β1-induced ECM deposition and the protective effects of CTRP6 on FAO could be abolished by compound C, a selective inhibitor of AMPK. Compound C also reversed the CTRP6-mediated upregulation of p-AMPK. The mediation of FAO by CTRP6 plays a key role in kidney fibrosis by regulating TGF-β1-induced renal tubular epithelial cell differentiation by promoting FAO, which is mediated via AMPK activation.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Role of the CTRP6/AMPK pathway in kidney fibrosis through the promotion of fatty acid oxidation

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief