The role of the renin‐angiotensin system in skin physiology and pathophysiology

Abstract

From the early days until now, textbook knowledge and research about the renin-angiotensin system (RAS) have focused on the renal, vascular and central effects of the main effector hormone of the system, angiotensin II (Ang II). It is still widely unknown that all the RAS components are also expressed in skin, which is why working on the cutaneous RAS is sometimes like being caught between two stools: the scientific RAS community regards the skin as irrelevant as a target organ for the RAS and the dermatology/skin research community regards the RAS as irrelevant for skin physiology and pathophysiology. Despite this hindrance, the number of publications on the cutaneous RAS has steadily risen since the first description of the expression of all components of the RAS in rodent and human skin and is now in the hundreds. [1,2] These studies have provided strong evidence that the RAS is in fact

Emerging importance of ACE2 in external stratified epithelial tissues

“…This paper will review the presence of tissue RAS in skin and cornea, two distinct stratified squamous epithelial tissues with somewhat overlapping properties and will primarily focus on the critical roles of Ang II and ACE2 in wound healing and inflammation. Since there is a recent review on the functions of RAS and its pathophysiology in skin ( Silva, Assersen, Willadsen et al, 2020 ), we will focus our attention more to our recent findings in the cornea ( Wang, Kaplan, Wysocki et al, 2020 ) as well as potential implications of interactions of SARS-CoV-2 and ACE2 in the cornea of patients with COVID-19. Thus, understanding the biology of ACE2 in the context of the cornea and skin is exceedingly timely.…”

“…The expression of the components of RAS in skin has been well documented ( Silva et al, 2020 , Nehme, Cerutti, Dhaouadi et al, 2015 ). RAS components are expressed in epidermis, dermal fibroblasts, dermal vessel walls, subcutaneous fat, and human hair follicles as well as in cultured primary keratinocytes, melanocytes, and dermal microvascular endothelial cells ( Takeda, Katagata and Kondo, 2002 , Steckelings, Wollschlager, Peters et al, 2004 , Aleksiejczuk, Gromotowicz-Poplawska, Marcinczyk et al, 2019 ).…”

In search of the needle in a haystack: Finding a suitable serum biomarker for monitoring disease activity of systemic sclerosis

“…Targeting the renin‐angiotensin system by pharmacological inhibitors is another potential antifibrotic pathway in SSc, keloids and related fibrotic disorders 104,105 …”

“…Interestingly, attenuation of intracellular ROS signalling, in part by altering mitochondrial oxidative phosphorylation appears to be involved in the antifibriotic actions of both α‐MSH and α7nAChR agonists. It is hoped that targeting such neuroendocrine pathways with specific pharmacological agents can add novel disease‐modifying therapies to patients with SSc 98,104,113 …”

Towards a renaissance of dermatoendocrinology: Selected current frontiers

“…Moving away from steroid hormones, Silva et al [62] elegantly continue and elaborate on a discussion that the senior author had started on the pages of this journal a quarter of a century ago, [15] namely how does activation of the renin‐angiotensin system (RAS) and its key components, that is angiotensin II, angiotensin AT 1 and AT 2 receptors and angiotensin‐converting enzyme (ACE), impact on skin physiology and pathology, and why is this of clincial relevance? The authors explain why the RAS invites novel interventions in dermatological therapy that still await systematic preclinical and clinical exploration.…”