中国医学科学院聂宇团队宣布他们开发出靶向溶菌酶2在心内膜通过调节远程损伤信号促进快速恢复。2025年9月17日出版的《细胞—干细胞》杂志发表了这项成果。

该课题组观察到溶菌酶2 （Lyz2）在损伤的无主题心脏的局部损伤部位和远处区域异常高表达，而在非再生心脏的心内膜细胞中，Lyz2的表达明显保持不变。虽然传统上被认为是髓系标志物，但小组证明LYZ2是一种损伤特异性的、溶酶体降解能力的正调节因子，介导细胞外基质的致病性降解。在小鼠和人心肌内膜实验模型中，该课题组观察到破坏LYZ2/LYZ功能对CMs具有抗凋亡作用。利用这些见解，研究人员表明Lyz2敲除（KO）和溶酶体降解的药理抑制都能使受伤的非再生心脏快速功能恢复。他们针对非CM细胞类型的远程损伤反应，迅速促进非再生心脏的心肌梗死后恢复。

研究人员表示，成年哺乳动物的心脏是不可再生的，大多数研究心肌梗死（MI）后的修复和潜在再生的研究都集中在心肌细胞（CM）增殖和梗死区。

附：英文原文

Title: Targeting lysozyme 2 in endocardium promotes rapid recovery by modulating remote injury signals

Author: Chenghao Fan, Shen Song, Yu Han, Dongcheng Cai, Anteng Shi, Fangfang Wan, Jie Feng, Jiajun Zhong, Yifan Xie, Fei Xu, Jiangping Song, Shengshou Hu, Yu Nie, Hui Zhang

Issue&Volume: 2025-09-17

Abstract: Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (Lyz2) in injured mouse hearts at both local injury sites and at remote zones, with sustained Lyz2 expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both Lyz2 knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.

DOI: 10.1016/j.stem.2025.08.015

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00330-3