Department of Preclinical Safety, Novartis Institutes for Biomedical Research, Klybeckstrasse 141, 4057, Basel, Switzerland.
J Mol Histol. 2013 Dec;44(6):733-47. doi: 10.1007/s10735-013-9524-5. Epub 2013 Jul 24.
Dipeptidyl peptidase IV (DPP4) is a peptidase whose inhibition is beneficial in Type II diabetes treatment. Several evidences suggest potential implication of DPP4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases where its inhibition could also be beneficial. DPP4 expression in human skin was described mainly in dermal fibroblasts and a subset of keratinocytes in the basal layer. Of importance in the perspective of preclinical experimentation, DPP4 distribution in skin of non-human primate species has not been documented. This report evidences unexpected differences between a set of human and cynomolgus monkey skin samples revealing a major expression of DPP4 in eccrine sweat glands of cynomolgus monkeys but not in humans. This represents a unique distinctive feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors (NPY-receptor 1 and Neurokinin receptor). Finally the observation that cathepsin D, an unrelated protease, shows the opposite expression compared to DPP4 (present in human but not in cynomolgus monkey eccrine sweat glands) could indicate that human eccrine sweat glands evolved a divergent protease repertoire compared to non-human primates. These unexpected differences in the eccrine sweat glands protease repertoire will need to be confirmed extending the analysis to a major number of donors but could imply possible biochemical divergences, reflecting the functional evolution of the glands and the control of their activity. Our findings also demonstrate that non-human primates studies aiming at understanding DPP4 function in skin biology are not readily translatable to human.
二肽基肽酶 4（DPP4）是一种肽酶，其抑制作用有益于 2 型糖尿病的治疗。有几项证据表明 DPP4 可能与皮肤疾病有关，如银屑病、瘢痕疙瘩和纤维化皮肤病，其抑制作用也可能有益。DPP4 在人类皮肤中的表达主要在真皮成纤维细胞和基底层的一部分角质形成细胞中。从临床前实验的角度来看，尚未记录非人类灵长类动物皮肤中 DPP4 的分布。本报告证明了一组人类和食蟹猴皮肤样本之间存在出乎意料的差异，揭示了 DPP4 在食蟹猴的外分泌汗腺中大量表达，但在人类中没有表达。与二肽基肽酶 8 和 9 的保守表达以及潜在相关的 DPP4 底物（如神经肽 Y（NPY）和受体（NPY 受体 1 和神经激肽受体）相比，这是一个独特的特征。最后，观察到组织蛋白酶 D，一种不相关的蛋白酶，与 DPP4 的表达相反（存在于人类中，但不存在于食蟹猴的外分泌汗腺中），这表明人类外分泌汗腺与非人类灵长类动物相比进化出了不同的蛋白酶谱。需要通过对更多供体进行分析来确认外分泌汗腺蛋白酶谱中的这些意外差异，但这可能意味着可能存在生化差异，反映了腺体的功能进化和对其活动的控制。我们的发现还表明，旨在了解 DPP4 在皮肤生物学中的功能的非人类灵长类动物研究不易转化为人类。
