Department of Cardiovascular & Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Department of Dermatology, Odense University Hospital, Odense, Denmark.
Am J Physiol Cell Physiol. 2023 Mar 1;324(3):C741-C756. doi: 10.1152/ajpcell.00269.2022. Epub 2023 Feb 6.
Vasoactive peptides often serve a multitude of functions aside from their direct effects on vasodynamics. This article will review the existing literature on two vasoactive peptides and their involvement in skin homeostasis: adiponectin and-as the main representative of the kallikrein-kinin system-bradykinin. Adiponectin is the most abundantly expressed adipokine in the human organism, where it is mainly localized in fat depots including subcutaneous adipose tissue, from where adiponectin can exert paracrine effects. The involvement of adiponectin in skin homeostasis is supported by a number of studies reporting the effects of adiponectin in isolated human keratinocytes, sebocytes, fibroblasts, melanocytes, and immune cells. Regarding skin pathology, the potential involvement of adiponectin in psoriasis, atopic dermatitis, scleroderma, keloid, and melanogenesis is discussed in this article. The kallikrein-kinin system is composed of a variety of enzymes and peptides, most of which have been identified to be expressed in the skin. This also includes the expression of bradykinin receptors on most skin cells. Bradykinin is one of the very few hormones that is targeted by treatment in routine clinical use in dermatology-in this case for the treatment of hereditary angioedema. The potential involvement of bradykinin in wound healing, psoriasis, and melanoma is further discussed in this article. This review concludes with a call for additional preclinical and clinical studies to further explore the therapeutic potential of adiponectin supplementation (for psoriasis, atopic dermatitis, wound healing, scleroderma, and keloid) or pharmacological interference with the kallikrein-kinin system (for wound healing, psoriasis, and melanoma).
血管活性肽除了对血管动力学有直接影响外，通常还具有多种功能。本文将回顾两种血管活性肽的现有文献及其在皮肤稳态中的作用：脂联素和缓激肽，作为激肽释放酶-激肽系统的主要代表。脂联素是人体中表达最丰富的脂肪因子，主要定位于包括皮下脂肪组织在内的脂肪组织中，脂联素可以从那里发挥旁分泌作用。许多研究报告了脂联素对分离的人角质形成细胞、皮脂细胞、成纤维细胞、黑素细胞和免疫细胞的作用，支持了脂联素在皮肤稳态中的作用。关于皮肤病理学，本文讨论了脂联素在银屑病、特应性皮炎、硬皮病、瘢痕疙瘩和黑色素生成中的潜在作用。激肽释放酶-激肽系统由多种酶和肽组成，其中大多数已被鉴定在皮肤中表达。这还包括大多数皮肤细胞上缓激肽受体的表达。缓激肽是少数几种在皮肤科常规临床治疗中靶向治疗的激素之一——在这种情况下，用于治疗遗传性血管性水肿。本文进一步讨论了缓激肽在伤口愈合、银屑病和黑色素瘤中的潜在作用。本文的结论是呼吁进行更多的临床前和临床研究，以进一步探索脂联素补充（用于银屑病、特应性皮炎、伤口愈合、硬皮病和瘢痕疙瘩）或药理学干预激肽释放酶-激肽系统（用于伤口愈合、银屑病和黑色素瘤）的治疗潜力。
