From the Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine; the Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School; and the Department of Civil and Environmental Engineering, Stanford University School of Engineering.
Plast Reconstr Surg. 2019 Jul;144(1):58e-67e. doi: 10.1097/PRS.0000000000005717.
Fibroproliferative disorders result in excessive scar formation, are associated with high morbidity, and cost billions of dollars every year. Of these, keloid disease presents a particularly challenging clinical problem because the cutaneous scars progress beyond the original site of injury. Altered mechanotransduction has been implicated in keloid development, but the mechanisms governing scar progression into the surrounding tissue remain unknown. The role of mechanotransduction in keloids is further complicated by the differential mechanical properties of keloids and the surrounding skin.
The authors used human mechanical testing, finite element modeling, and immunohistologic analyses of human specimens to clarify the complex interplay of mechanical stress, strain, and stiffness in keloid scar progression.
Changes in human position (i.e., standing, sitting, and supine) are correlated to dynamic changes in local stress/strain distribution, particularly in regions with a predilection for keloids. Keloids are composed of stiff tissue, which displays a fibrotic phenotype with relatively low proliferation. In contrast, the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via rho kinase mechanotransduction pathway and elevated inflammation and proliferation, which may lead to keloid progression.
The authors conclude that changes in human position are strongly correlated with mechanical loading of the predilection sites, which leads to increased mechanical strain in the peripheral tissue surrounding keloids. Furthermore, increased mechanical strain in the peripheral tissue, which is the site of keloid progression, was correlated with aberrant expression of caveolin-1/ROCK signaling pathway. These findings suggest a novel mechanism for keloid progression.
纤维增生性疾病会导致过度的疤痕形成，与高发病率相关，并每年耗费数十亿美元。其中，瘢痕疙瘩病呈现出特别具有挑战性的临床问题，因为皮肤疤痕会超出最初的损伤部位进展。机械信号转导的改变与瘢痕疙瘩的发展有关，但控制疤痕向周围组织进展的机制尚不清楚。机械信号转导在瘢痕疙瘩中的作用因瘢痕疙瘩和周围皮肤的机械性能差异而变得更加复杂。
作者使用人体力学测试、有限元建模和人体标本的免疫组织化学分析，阐明了机械应力、应变和硬度在瘢痕疙瘩进展中的复杂相互作用。
人体位置的变化（即站立、坐着和仰卧）与局部应力/应变分布的动态变化相关，特别是在容易出现瘢痕疙瘩的区域。瘢痕疙瘩由硬组织组成，表现出纤维化表型，增殖相对较低。相比之下，位于瘢痕疙瘩周围的柔软皮肤会受到高机械应变的影响，这与通过 Rho 激酶机械信号转导途径的 caveolin-1/ Rho 信号的表达增加以及炎症和增殖的增加相关，这可能导致瘢痕疙瘩的进展。
作者得出结论，人体位置的变化与易患部位的机械负荷密切相关，这会导致瘢痕疙瘩周围的外围组织的机械应变增加。此外，外围组织中增加的机械应变是瘢痕疙瘩进展的部位，与 caveolin-1/ROCK 信号通路的异常表达相关。这些发现为瘢痕疙瘩的进展提供了一种新的机制。
