Differential expression of angiotensin receptors in human cutaneous wound healing

Steckelings, Ulrike Muscha; Henz, Beate M.; Wiehstutz, S.; Unger, Thomas; Artuc, Metin

doi:10.1111/j.1365-2133.2005.06806.x

Cited by 72 publications

(63 citation statements)

References 48 publications

(76 reference statements)

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“…Ang II stimulates proliferation, migration and matrix production of human dermal fibroblasts (19)(20)(21)(22). Immunohistochemical staining of normal skin, wounded skin and hypertrophic scars has revealed that AT 1 and AT 2 expression are increased in scar epithelium and endothelium and that angiotensin-converting enzymes (ACE) activity is also increased, but reports of these findings do not describe immunostaining of the deep dermis (15,16). Administration of Ang II and its nonhypertensive analog angiotensin (1-7) accelerates dermal repair in rodents (23,24).…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

Bond

Bergeron

Thurlow

et al. 2011

Mol Med

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Aberrant fibroblast migration in response to fibrogenic peptides plays a significant role in keloid pathogenesis. Angiotensin II (Ang II) is an octapeptide hormone recently implicated as a mediator of organ fibrosis and cutaneous repair. Ang II promotes cell migration but its role in keloid fibroblast phenotypic behavior has not been studied. We investigated Ang II signaling in keloid fibroblast behavior as a potential mechanism of disease. Primary human keloid fibroblasts were stimulated to migrate in the presence of Ang II and Ang II receptor 1 (AT 1 ), Ang II receptor 2 (AT 2 ) or nonmuscle myosin II (NMM II) antagonists. Keloid and the surrounding normal dermis were immunostained for NMM IIA, NMM IIB, AT 2 and AT 1 expression. Primary human keloid fibroblasts were stimulated to migrate with Ang II and the increased migration was inhibited by the AT 1 antagonist EMD66684, but not the AT 2 antagonist PD123319. Inhibition of the promigratory motor protein NMM II by addition of the specific NMM II antagonist blebbistatin inhibited Ang II-stimulated migration. Ang II stimulation of NMM II protein expression was prevented by AT 1 blockade but not by AT 2 antagonists. Immunostaining demonstrated increased NMM IIA, NMM IIB and AT 1 expression in keloid fibroblasts compared with scant staining in normal surrounding dermis. AT 2 immunostaining was absent in keloid and normal human dermal fibroblasts. These results indicate that Ang II mediates keloid fibroblast migration and possibly pathogenesis through AT 1 activation and upregulation of NMM II.

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Section: Introductionmentioning

confidence: 99%

“…Ang II also acts locally to promote tissue repair in the vasculature, heart, brain, lung, kidney, liver and skin (13)(14)(15)(16). In mammalian cells, Ang II signals through two principal receptors, angiotensin receptor 1 (AT 1 ) and angiotensin receptor 2 (AT 2 ) (12).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

Bond

Bergeron

Thurlow

et al. 2011

Mol Med

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“…AT 2 Rs are expressed in the human skin (throughout the epidermal and dermal structures) 14 and are markedly upregulated in incisional cutaneous wounds. 15 AT 2 Rs have been demonstrated in the human coronary microcirculation, where they may contribute to vasodilation. 16 Studies in cellular and animal models suggest that AT 2 R counteracts many AT 1 R actions by inducing vasodilation, antiproliferation, and apoptosis.…”

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confidence: 99%

Angiotensin Type 2 Receptor in Resistance Arteries of Type 2 Diabetic Hypertensive Patients

et al. 2007

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Abstract-The role of angiotensin type 2 receptor (AT 2 R) on vascular responses to angiotensin II in humans remains unclear. In this study we explored whether AT 2 R is expressed and functionally active on peripheral resistance arteries of hypertensive diabetic patients treated for 1 year with either the angiotensin receptor blocker valsartan or the ␤-blocker atenolol. Twenty-six hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving angiotensin receptor blockers or ␤-blockers) were randomly assigned to double-blind treatment for 1 year with valsartan or atenolol once daily added to their previous therapy in a clinical trial that we reported recently and compared with 10 normal subjects. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. Vasomotor response curves to angiotensin II (1 nmol/L to 1 mol/L) were performed on norepinephrine precontracted vessels in the presence of valsartan (10 mol/L) with or without the AT 2 R inhibitor PD123319 (1 mol/L). AT 2 R expression was evaluated by confocal microscopy. After 1 year of treatment, systolic and diastolic blood pressure was controlled and comparable in the valsartan and atenolol groups. Angiotensin II evoked a significant vasodilatory response only on resistance arteries from patients treated with valsartan, effect blocked by PD123319. AT 2 R expression was 4-fold higher in small arteries of valsartan-treated patients. A ngiotensin II (Ang II) is the main biological effector of the renin-angiotensin system, which plays a major role in cardiovascular and renal homeostasis. Most of the physiological and pathophysiological effects of Ang II are mediated by the angiotensin type 1 receptor (AT 1 R), which is widely expressed by most cell types. Expression of the angiotensin type 2 receptor (AT 2 R) is more limited and occurs predominantly in fetal tissues where it may play a role during development. 1,2 Recent studies, mostly in cellular and adult animal models, mapped the distribution of AT 2 R in certain areas of the brain, 3 kidneys, 4 coronary arteries, cardiomyocytes, ventricular myocardium, 5 and the vasculature. 6,7 Increased AT 2 R expression has been observed under pathological conditions, such as vascular injury, 8 hypertension, 6,7 myocardial infarction, 9,10 congestive heart failure, 11 renal failure, 12 and brain ischemia. 13 Few studies have investigated the functional expression of AT 2 R in humans. AT 2 Rs are expressed in the human skin (throughout the epidermal and dermal structures) 14 and are markedly upregulated in incisional cutaneous wounds. 15 AT 2 Rs have been demonstrated in the human coronary microcirculation, where they may contribute to vasodilation. 16 Studies in cellular and animal models suggest that AT 2 R counteracts many AT 1 R actions by inducing vasodilation, antiproliferation, and apoptosis. 2 We showed recently in animal models of hypertension that AT 2 R is upregulated and mediates vasodilation only when AT 1 Rs are bl...

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“…74 Consistently, vasorelaxation mediated by the AT 2 receptor was demonstrated in isolated human coronary microarteries using myography. 106 Furthermore, an upregulation of AT 2 receptors in the human species can be observed under pathological conditions such as skin injury ex vivo 107 and heart failure in vivo. 108 The discrepancies concerning the functional role of the AT 2 receptor discussed above may also be resolved by a model in which not the receptor per se is 'good' or 'evil', but in which the type of adapter protein recruited to the receptor determines the cellular effects (figures 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Adapter proteins and promoter regulation of the angiotensin AT2 receptor — implications for cardiac pathophysiology

Funke-Kaiser

Reinemund

Steckelings

et al. 2009

J Renin Angiotensin Aldosterone Syst

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The angiotensin AT 2 receptor (AT 2 R) represents an important component of the renin-angiotensin system since it is involved in the (patho) physiology of different cardiovascular and neuronal diseases. Furthermore, AT 2 receptors can partly mediate beneficial effects of angiotensin AT 1 receptor (AT 1 R) blockers, and direct pharmacological AT 2 receptor agonism emerges as a novel therapeutic strategy. This review discusses the constitutive and ligand-mediated activity as well as the signal transduction of the AT 2 receptor, focusing on adapter proteins which directly bind to this receptor. Direct protein-protein interaction partners of the AT 2 receptor described so far include the transcription factor promyelocytic zinc finger protein, AT 2 receptor binding protein and the AT 1 receptor. In addition, the putative crosstalk of the AT 2 receptor with the renin/ prorenin receptor (RER) via the promyelocytic zinc finger protein (PLZF) and the role of oestrogens on the regulation of the AT 2 receptor are presented. Conceiving the coupling of the AT 2 receptor to different adapter proteins with distinct and partly opposing cellular effects and the implications of its constitutive activity might help to overcome the current controversies on the (patho)physiological role of the AT 2 receptor.

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Differential expression of angiotensin receptors in human cutaneous wound healing

Abstract: From these data, we conclude that angiotensin AT1 and AT2 receptors are upregulated in human cutaneous wounds, giving further support to the concept that angiotensin II plays a role even at an early stage during cutaneous wound healing.

Cited by 72 publications

References 48 publications

Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

Angiotensin Type 2 Receptor in Resistance Arteries of Type 2 Diabetic Hypertensive Patients

Adapter proteins and promoter regulation of the angiotensin AT2 receptor — implications for cardiac pathophysiology

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