清华大学陈婷小组在研究中取得进展。他们开发出皮肤的机械阻力机制与陆地运动相适应。2025年8月4日，国际知名学术期刊《细胞》发表了这一成果。

课题组在皮肤上皮细胞中发现了一种适应这种机械需求的进化机制。研究人员发现在四足动物中保守的Slurp1基因在掌跖皮肤中特异性表达。在人类中，SLURP1的突变会导致掌跖角化病（PPK），这是一种以脚底和手掌的皮肤表皮病理性增厚为特征的疾病。值得注意的是，减少Slurp1基因敲除爪子皮肤上的机械压力完全恢复了PPK表型。在机制上，SLURP1定位于内质网（ER）膜，在那里它与钙泵SERCA2b结合。通过在机械压力下保持SERCA2b活性，SLURP1维持低细胞质钙水平，抑制压力诱导的pPERK-NRF2信号激活，这是一种可以通过基因靶向逆转PPK的途径。这些发现揭示了基于内质网的机械阻力机制，增强了细胞对长时间机械压力的防御。

据了解，从水到陆地的过渡需要动物进化出特殊的爪子皮肤来支撑身体重量并使其能够运动。

附：英文原文

Title: A mechano-resistance mechanism in skin adapts to terrestrial locomotion

Author: Ruonan Di, Qianqian Du, Yuhua Xie, Yanhua Lu, Wenxuan Gao, Lei Zhang, Xiaoli Qi, Yanyan Fan, Jiao Li, Fengchao Wang, She Chen, Ting Chen

Issue&Volume: 2025-08-04

Abstract: The transition from water to land required animals to evolve specialized paw skin to support body weight and enable locomotion. We identify an evolutionarily emerged mechanism in skin epithelial cells that adapts to this mechanical demand. We show that the Slurp1 gene, conserved across tetrapods, is specifically expressed in palmoplantar skin. In humans, mutations in SLURP1 cause palmoplantar keratoderma (PPK), a condition marked by pathologically thickened skin epidermis on the soles and palms. Remarkably, reducing mechanical pressure on Slurp1 knockout paw skin fully rescues the PPK phenotype. Mechanistically, SLURP1 localizes to the endoplasmic reticulum (ER) membrane, where it binds the calcium pump SERCA2b. By preserving SERCA2b activity under mechanical pressure, SLURP1 maintains low cytoplasmic calcium levels and inhibits pressure-induced activation of the pPERK-NRF2 signaling—a pathway that can be genetically targeted to reverse PPK. These findings reveal an ER-based mechano-resistance mechanism that enhances cellular defense against prolonged mechanical pressure.

DOI: 10.1016/j.cell.2025.07.012

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00801-3