scholarly journals Intrarenal Renin–Angiotensin System Involvement in the Pathogenesis of Chronic Progressive Nephropathy—Bridging the Informational Gap Between Disciplines

2019 ◽  
Vol 47 (7) ◽  
pp. 799-816 ◽  
Author(s):  
Leslie A. Obert ◽  
Kendall S. Frazier
Keyword(s):  
Protein Interactions ◽  
Transforming Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Critical Pathway ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Related ◽  
Using Data

Chronic progressive nephropathy (CPN) is the most commonly encountered spontaneous background finding in laboratory rodents. Various theories on its pathogenesis have been proposed, but there is a paucity of data regarding specific mechanisms or physiologic pathways involved in early CPN development. The current CPN mechanism of action for tumorigenesis is largely based on its associated increase in tubular cell proliferation without regard to preceding subcellular degenerative changes. Combing through the published literature from multiple biology disciplines provided insight into the preceding cellular events. Mechanistic pathways involved in the progressive age-related decline in rodent kidney function and several key inflexion points have been identified. These critical pathway factors were then connected using data from renal models from multiple rodent strains, other species, and mechanistic work in humans to form a cohesive picture of pathways and protein interactions. Abundant data linked similar renal pathologies to local events involving hypoxia (hypoxia-inducible factor 1α), altered intrarenal renin–angiotensin system (RAS), oxidative stress (nitric oxide), and pro-inflammatory pathways (transforming growth factor β), with positive feedback loops and downstream effectors amplifying the injury and promoting scarring. Intrarenal RAS alterations seem to be central to all these events and may be critical to CPN development and progression.

scholarly journals Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys

2018 ◽  
Vol 19 (3) ◽  
pp. 147032031880300 ◽  
Author(s):  
Chung-Ming Chen ◽  
Shu-Hui Juan ◽  
Hsiu-Chu Chou
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Angiotensin System ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Renin Angiotensin ◽  
Factor Α

Introduction: The renin–angiotensin system and epithelial–mesenchymal transition play crucial roles in the development of kidney fibrosis. The connection between the renin–angiotensin system and transforming growth factor-β in epithelial–mesenchymal transition remains largely unknown. Materials and methods: We assessed oxidative stress, cytokine levels, renal morphology, profibrotic growth factor and renin–angiotensin system component expression, and cell-specific E- and N-cadherin expression in the kidneys of gerbils with streptozotocin-induced diabetes mellitus. Results: Animals in the experimental group received an intraperitoneal injection of streptozotocin to induce diabetes. The diabetic gerbil kidneys presented kidney injury, which was manifested as distorted glomeruli, necrosis of tubular cells, dilated tubular lumen, and brush border loss. Additionally, the diabetic gerbil kidneys exhibited significantly higher expressions of 8-hydroxy-2′-deoxyguanosine, nuclear factor-kB, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and N-cadherin and higher collagen deposition than did the control gerbil kidneys. Compared with the control kidneys, the diabetic gerbil kidneys exhibited significantly lower E-cadherin expression. These epithelial–mesenchymal transition characteristics were associated with an increase in renin–angiotensin system expression in the diabetic gerbils. Conclusions: We demonstrate that hyperglycemia activated the renin–angiotensin system, induced epithelial–mesenchymal transition, and contributed to kidney fibrosis in an experimental diabetes mellitus model.

scholarly journals Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment

2020 ◽  
Author(s):  
Daan C.H. van Dorst ◽  
Nathalie P. de Wagenaar ◽  
Ingrid van der Pluijm ◽  
Jolien W. Roos-Hesselink ◽  
Jeroen Essers ◽  
...  
Keyword(s):  
Growth Factor ◽  
Medical Treatment ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Aortic Aneurysms ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Thoracic Aortic Aneurysms ◽  
Β Blockers

AbstractThoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta, which can lead to life-threatening complications, such as aortic dissection and rupture. TAAs frequently occur in a syndromic form in individuals with an underlying genetic predisposition, such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Increasing evidence supports an important role for transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS) in TAA pathology. Eventually, most patients with syndromic TAAs require surgical intervention, as the ability of present medical treatment to attenuate aneurysm growth is limited. Therefore, more effective medical treatment options are urgently needed. Numerous clinical trials investigated the therapeutic potential of angiotensin receptor blockers (ARBs) and β-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-β signaling, RAS, and impaired mechanosensing abilities of aortic VSMCs in TAA formation. Furthermore, it critically discusses the most recent clinical evidence regarding the possible therapeutic benefit of ARBs and β-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.

Postnatal development of the renin-angiotensin system in rats

1980 ◽  
Vol 238 (5) ◽  
pp. R432-R437 ◽  
Author(s):  
K. B. Wallace ◽  
J. B. Hook ◽  
M. D. Bailie
Keyword(s):  
Steady State ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Neonatal Rat ◽  
Postnatal Life ◽  
Renin Substrate ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Related

The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity.

scholarly journals Alisol B 23-acetate attenuates CKD progression by regulating the renin–angiotensin system and gut–kidney axis

2020 ◽  
Vol 11 ◽  
pp. 204062232092002
Author(s):  
Hua Chen ◽  
Min-Chang Wang ◽  
Yuan-Yuan Chen ◽  
Lin Chen ◽  
Yan-Ni Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gut Microbiome ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Renin Angiotensin System ◽  
Ckd Progression ◽  
Angiotensin System ◽  
Mesenchymal Transition ◽  
Renin Angiotensin

Background: Increasing evidence suggests a link between the gut microbiome and various diseases including hypertension and chronic kidney disease (CKD). However, studies examining the efficacy of controlling blood pressure and inhibiting the renin–angiotensin system (RAS) in preventing CKD progression are limited. Methods: In the present study, we used 5/6 nephrectomised (NX) and unilateral ureteral obstructed (UUO) rat models and cultured renal tubular epithelial cells and fibroblasts to test whether alisol B 23-acetate (ABA) can attenuate renal fibrogenesis by regulating blood pressure and inhibiting RAS. Results: ABA treatment re-established dysbiosis of the gut microbiome, lowered blood pressure, reduced serum creatinine and proteinuria, suppressed expression of RAS constituents and inhibited the epithelial-to-mesenchymal transition in NX rats. Similarly, ABA treatment inhibited expression of collagen I, fibronectin, vimentin, α-smooth muscle actin and fibroblast-specific protein 1 at both mRNA and protein levels in UUO rats. ABA was also effective in suppressing activation of the transforming growth factor-β (TGF-β)/Smad3 and preserving Smad7 expression in both NX and UUO rats. In vitro experiments demonstrated that ABA treatment inhibited the Wnt/β-catenin and mitochondrial-associated caspase pathways. Conclusion: These data suggest that ABA attenuated renal fibrosis through a mechanism associated with re-establishing dysbiosis of the gut microbiome and regulating blood pressure, and Smad7-mediated inhibition of Smad3 phosphorylation. Thus, we demonstrate ABA as a promising candidate for treatment of CKD by improving the gut microbiome and regulating blood pressure.

scholarly journals The renin–angiotensin system and prevention of age-related functional decline: where are we now?

AGE ◽  
2015 ◽  
Vol 37 (1) ◽  
Author(s):  
Corey B. Simon ◽  
Brittany Lee-McMullen ◽  
Dane Phelan ◽  
Janine Gilkes ◽  
Christy S. Carter ◽  
...  
Keyword(s):  
Functional Decline ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Related

scholarly journals EXACERBATED AGE-RELATED OBESITY IS TEMPERED BY RENIN ANGIOTENSIN SYSTEM

2017 ◽  
Vol 1 (suppl_1) ◽  
pp. 580-580
Author(s):  
E. Bruce ◽  
C.S. Carter ◽  
Y. Sakarya ◽  
H.Z. Toklu ◽  
D. Morgan ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Related
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