Atrophic acne scar: a process from altered metabolism of elastic fibres and collagen fibres based on transforming growth factor‐β1 signalling

Abstract

Summary Background Atrophic acne scar, a persistent sequela from acne, is undesirably troubling to many patients due to its cosmetic and psychosocial aspects. Although there have been some reports emphasizing the role of early inflammatory responses in atrophic acne scarring, evolving perspectives on the detailed pathogenic processes are promptly needed. Objectives Examining the histological, immunological and molecular changes in early acne lesions susceptible to atrophic scarring can provide new insights to understand the pathophysiology of atrophic acne scar. Methods We experimentally validated several early fundamental hallmarks accounting for the transition of early acne lesions to atrophic scars by comparing molecular profiles of skin and acne lesions between patients who were prone to scar (APS) or not (ANS). Results In APS, compared with ANS, devastating degradation of elastic fibres and collagen fibres occurred in the dermis, followed by their incomplete recovery. Abnormally excessive inflammation mediated by innate immunity with T helper 17 and T helper 1 cells was observed. Epidermal proliferation was significantly diminished. Transforming growth factor (TGF)‐β1 was drastically elevated in APS, suggesting that aberrant TGF‐β1 signalling is an underlying modulator of all of these pathological processes. Conclusions These results may provide a basis for understanding the pathogenesis of atrophic acne scarring. Reduction of excessive inflammation and TGF‐β1 signalling in early acne lesions is expected to facilitate the protection of normal extracellular matrix metabolism and ultimately the prevention of atrophic scar formation. What's already known about this topic? The dermis of atrophic acne scars shows alteration of extracellular matrix components such as collagen fibres. Inflammation in acne lesions is associated with the development of acne scars. What does this study add? Abnormalities in the metabolism of collagen fibres and elastic fibres were observed in the early developmental stages of acne lesions that were progressing into atrophic scars. Exacerbated inflammation and aberrant epidermal proliferation by increased transforming growth factor (TGF)‐β1 signalling may affect the abnormal extracellular matrix metabolism. What is the translational message? Abnormal changes in elastic fibres and collagen fibres are found in the early developmental process of acne in patients who are prone to atrophic scarring. An early treatment regimen strongly inhibiting inflammation and TGF‐β1 signalling to help the normal recovery of the extracellular matrix components is required to prevent atrophic scarring.

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“…14,15 Furthermore, our previous clinical studies found that the injection of BTA in the early postoperative can decrease the scar formation and reduce the scar width in median sternotomy wound. Many studies have demonstrated that BTA not only reduces the wound tension to decrease scar formation, but also prevents the excessive deposition of collagen, 16,17 which was confirmed in the present study. These previous studies indicate that BTA is involved in the scar fibrosis process.…”

Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis

“…Transforming growth factor-β (TGFβ), IL-6, MMP, IGF-1, and B cells are found in keloid/hypertrophic scar tissues [ 37 , 38 ]. In atrophic scars, TLR4, IL-2, IL-10, tissue inhibitor of metalloprotease 2 (TIMP2), JUN, and TGFβ are elevated [ 39 , 40 ]. Immunological responses are different between patients with and without scarring [ 15 ].…”

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“…It arises from disorganised production and deposition of collagen in the dermis resulting in visibly depressed scars. The major types of atrophic scars are boxcar, ice pick, and rolling scars 25,32,33 . To date, with various patterns and profiles, there is no uniform treatment for acne scar 3,31,34 .…”