Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio av. 7, LT-10257 Vilnius, Lithuania.
Systems Biology Lab, Amsterdam Institute for Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HZ Amsterdam, the Netherlands; Center for Quantitative Analysis of Cellular and Molecular Biosystems (BioQuant), Universität Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
J Photochem Photobiol B. 2021 May;218:112183. doi: 10.1016/j.jphotobiol.2021.112183. Epub 2021 Mar 29.
Photodynamic therapy is an attractive technique for various skin tumors and non-cancerous skin lesions. However, while the aim of photodynamic therapy is to target and damage only the malignant cells, it unavoidably affects some of the healthy cells surrounding the tumor as well. However, data on the effects of PDT to normal cells are scarce, and the characterization of the pathways activated after the photodamage of normal cells may help to improve clinical photodynamic therapy. In our study, primary human epidermal keratinocytes were used to evaluate photodynamic treatment effects of photosensitizers with different subcellular localization. We compared the response of keratinocytes to lysosomal photodamage induced by phthalocyanines, aluminum phthalocyanine disulfonate (AlPcS) or aluminum phthalocyanine tetrasulfonate (AlPcS), and cellular membrane photodamage by m-tetra(3-hydroxyphenyl)-chlorin (mTHPC). Our data showed that mTHPC-PDT promoted autophagic flux, whereas lysosomal photodamage induced by aluminum phthalocyanines evoked differentiation and apoptosis. Photodamage by AlPcS, which is targeted to lysosomal membranes, induced keratinocyte differentiation and apoptosis more efficiently than AlPcS, which is targeted to lysosomal lumen. Computational analysis of the interplay between these molecular pathways revealed that keratin 10 is the coordinating molecular hub of primary keratinocyte differentiation, apoptosis and autophagy.
光动力疗法是一种治疗各种皮肤肿瘤和非癌性皮肤病变的有吸引力的技术。然而，虽然光动力疗法的目的是靶向和仅损伤恶性细胞，但它不可避免地也会影响肿瘤周围的一些健康细胞。然而，关于光动力疗法对正常细胞的影响的数据很少，并且对正常细胞光损伤后激活的途径进行特征描述可能有助于改善临床光动力疗法。在我们的研究中，使用原代人表皮角质形成细胞来评估具有不同亚细胞定位的光敏剂的光动力治疗效果。我们比较了角质形成细胞对由酞菁、铝酞菁二磺酸钠（AlPcS）或铝酞菁四磺酸钠（AlPcS）诱导的溶酶体光损伤以及 m-四（3- 羟苯基）-卟啉（mTHPC）诱导的细胞膜光损伤的反应。我们的数据表明，mTHPC-PDT 促进自噬流，而铝酞菁引起的溶酶体光损伤则引发分化和凋亡。靶向溶酶体膜的 AlPcS 光损伤比靶向溶酶体腔的 AlPcS 更有效地诱导角质形成细胞分化和凋亡。这些分子途径之间相互作用的计算分析表明，角蛋白 10 是原代角质形成细胞分化、凋亡和自噬的协调分子枢纽。
