The mitochondrial component of intracrine action

In recent years the actions of intracellular-acting, extracellular signaling proteins/peptides (intracrines) have become increasingly defined. General principles of intracrine action have been proposed. Mitochondria represent one locus of intracrine action, and thus far, angiotensin II, transforming growth factor-β, growth hormone, atrial natriuretic peptide, Wnt 13, stanniocalcin, other renin-angiotensin system components, and vascular endothelial-derived growth factor, among others, have been shown to be mitochondria-localizing intracrines. The implications of this mitochondrial intracrine biology are discussed.

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

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320318803009 ◽

2018 ◽

Vol 19 (3) ◽

pp. 147032031880300 ◽

Cited By ~ 7

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.

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Nephrogenic systemic fibrosis is associated with transforming growth factor β and Smad without evidence of renin-angiotensin system involvement

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2008.02.038 ◽

2008 ◽

Vol 58 (6) ◽

pp. 1025-1030 ◽

Cited By ~ 26

Author(s):

Brent Kelly ◽

Matthew Petitt ◽

Ramon Sanchez

Keyword(s):

Growth Factor ◽

Nephrogenic Systemic Fibrosis ◽

Transforming Growth Factor ◽

Renin Angiotensin System ◽

Transforming Growth Factor Β ◽

Angiotensin System ◽

Renin Angiotensin ◽

System Involvement

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

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-020-07116-4 ◽

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.

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