EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways

Abstract

Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin–angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-β and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1β and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.

Chemical Composition and Antibacterial and Antiulcerative Colitis Activities of Essential Oil from Pruni Semen

“…58 The PI3K/AKT pathway is abnormally activated in DSS-induced UC, leading to enhanced expression and secretion of proinflammatory cytokines such as TNF-α, and finally induced mucosa injuries. 59 Overexpression of PI3K represents the activation of the PI3K/ AKT pathway, and the activated AKT translocates to the cytoplasm or nucleus to phosphorylate NF-κB and mTOR, MAPK (mainly the ERK subfamily), and a family of other substrates. 60 NF-κB serves as a pivotal signaling molecule in the pathogenesis of UC, inducing the production of substantial proinflammatory cytokines.…”

“…The involvement of the PI3K/AKT pathway in UC pathogenesis has been well documented . The PI3K/AKT pathway is abnormally activated in DSS-induced UC, leading to enhanced expression and secretion of proinflammatory cytokines such as TNF-α, and finally induced mucosa injuries . Overexpression of PI3K represents the activation of the PI3K/AKT pathway, and the activated AKT translocates to the cytoplasm or nucleus to phosphorylate NF-κB and mTOR, MAPK (mainly the ERK subfamily), and a family of other substrates .…”

Eicosapentaenoic acid-enriched phospholipids alleviate glucose and lipid metabolism in spontaneously hypertensive rats with CD36 mutation: a precise nutrition strategy

“…Similarly, Shi et al found that EPA-PLs alleviated hypertensive nephropathy by activating the PI3K/AKT pathway in the kidney tissue. 32 In addition, pro-inflammatory cytokines can cause insulin resistance in the adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. Interestingly, EPA and its lipid mediators are known to have an inflammation pro-resolution effect.…”

Downregulating ANGPTL3 by miR-144-3p promoted TGF-β1-induced renal interstitial fibrosis via activating PI3K/AKT signaling pathway

“…Renal interstitial fibrosis (RIF), a pivotal stage in the progression from CKD (chronic kidney disease) to ESRD (end-stage renal disease), is marked by an excessive accumulation of extracellular matrix proteins, the infiltration of inflammatory cells, and increased apoptosis in tubular epithelial cells [ 1 ]. Current therapeutic approaches for RIF are multifaceted, involving renin-angiotensin system inhibitors and lipid-lowering agents for blood pressure control, coupled with stringent dietary modifications [ 2 , 3 ]. While these measures have shown efficacy in preserving renal function, the incidence of ESRD continues to be substantial [ 4 ].…”