Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression

Abstract

Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling.

Diet in Intestinal Fibrosis: A Double-Edged Sword

“…Interestingly, the DHA effect was reinforced when combined with short chain fatty acid butyrate [ 84 ]. It is in accordance with a study from Zeng et al, showing that DHA inhibits TGF-β-induced rat renal fibroblast activation at a dose and time-dependent manner [ 85 ]. DHA derivative such as resolvin D1 was also evaluated in extra-intestinal fibrosis model [ 86 ].…”

The possible protective role of omega 3 on liver of L thyroxine treated male albino rats. Histological and immunhistochemical study

“…Zeng, yang et al 2017 [40] cited that omega3 can suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally [41] revealed that omega -3 PUFAs down-regulate the expression of profibrogenic genes in activated HSCs(hepatic stellate cells) and fibrotic liver.…”

Identification of the Perturbed Metabolic Pathways Associating With Renal Fibrosis and Evaluating Metabolome Changes of Pretreatment With Astragalus polysaccharide Through Liquid Chromatography Quadrupole Time-Of-Flight Mass Spectrometry

“…In addition, LysoPC can promote oxidative stress, inhibit glucose transport and insulin-mediated glucose metabolism, and inhibit the activity of Na + -K + -ATP enzyme, thus causing abnormalities in cell structure and function. The changes of LysoPCs are closely related to the renal fibrosis process and oxidative stress reaction in rats with renal fibrosis (Kang et al, 2015;Zeng et al, 2017;Sun et al, 2018;).…”