Attenuating Effects of Dieckol on Hypertensive Nephropathy in Spontaneously Hypertensive Rats.

Myeongjoo Son,Seyeon Oh,Junwon Choi,Ji Tae Jang,Kyunghee Byun,Kuk Hui Son

doi:10.3390/ijms22084230

Myeongjoo Son, Seyeon Oh + Show 4 more

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https://doi.org/10.3390/ijms22084230

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Abstract

Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.

Highlights

The kidney is a major organ that is affected by hypertensive target organ damage: chronic kidney disease commonly occurs in around 16% of hypertensive patients [1].The pathological features of hypertensive nephropathy include inflammation, glomerular sclerosis, tubular atrophy, and interstitial fibrosis [2]
Hypertensive nephropathy is typically described as nephroangiosclerosis and glomerular hyalinosis [24,25], recently, it was revealed that the interstitium of the kidney, which is involved in tubular interstitial fibrosis (TIF), is related to disease progression, as well as the glomerular and vascular compartments [26,27]
Since TIF is a main pathophysiology of hypertensive nephropathy, it is essential to the development of new agents directed to modulate TIF to prevent the progression of hypertensive nephropathy

Summary

Introduction

The pathological features of hypertensive nephropathy include inflammation, glomerular sclerosis, tubular atrophy, and interstitial fibrosis [2]. The fibrotic tissue replaces the normal functional kidney tissue, which leads to renal failure [3,4]. Renal fibrosis or tubular interstitial fibrosis is the main pathological lesion of hypertensive nephropathy, which induces end-stage renal disease (ESRD) [5]. Renal fibrosis shows the following characteristics: increased massive extracellular matrix (ECM) production, increased recruitment of fibroblasts to tissue injury sites, and increased phenotype changes from fibroblasts to α-smooth muscle actin (α-SMA)-expressing myofibroblasts [6]. The increased α-SMAexpressing myofibroblasts lead to the unnecessarily excessive deposition of collagen and enhance the dysregulation of matrix metalloproteinases, which destroys the basement membrane and further accelerates fibrosis [6]

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