Huang Shan, Shao Tinghui, Liu Hong, Li Tianfa, Gui Xianhua, Zhao Qianwen
Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Cardiology, Research Unit of Island Emergency Medicine of Chinese Academy of Medical Sciences, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
Front Cell Dev Biol. 2022 Feb 1;9:812748. doi: 10.3389/fcell.2021.812748. eCollection 2021.
Fibrosis is an evolutionarily conserved pathophysiological process serving bifurcated purposes. On the one hand, fibrosis is essential for wound healing and contributes to the preservation of organ function. On the other hand, aberrant fibrogenic response may lead to tissue remodeling and precipitate organ failure. Recently lineage tracing studies have shown that resident fibroblasts are the primary mediator of fibrosis taking place in key organs such as the heart, the lungs, and the kidneys. Megakaryocytic leukemia 1 (MKL1) is transcriptional regulator involved in tissue fibrosis. Here we generated resident fibroblast conditional MKL1 knockout (CKO) mice by crossing the mice to the -Cre mice. Models of cardiac fibrosis, pulmonary fibrosis, and renal fibrosis were reproduced in the CKO mice and wild type (WT) littermates. Compared to the WT mice, the CKO mice displayed across-the-board attenuation of fibrosis in different models. Our data cement the pivotal role MKL1 plays in tissue fibrosis but point to the cellular origin from which MKL1 exerts its pro-fibrogenic effects.
纤维化是一种具有进化保守性的病理生理过程，具有双重作用。一方面，纤维化对伤口愈合至关重要，并有助于维持器官功能。另一方面，异常的纤维生成反应可能导致组织重塑并促使器官衰竭。最近的谱系追踪研究表明，驻留成纤维细胞是心脏、肺和肾脏等关键器官中发生的纤维化的主要介质。巨核细胞白血病1（MKL1）是一种参与组织纤维化的转录调节因子。在这里，我们通过将小鼠与-Cre小鼠杂交，生成了驻留成纤维细胞条件性MKL1基因敲除（CKO）小鼠。在CKO小鼠和野生型（WT）同窝小鼠中重现了心脏纤维化、肺纤维化和肾纤维化模型。与WT小鼠相比，CKO小鼠在不同模型中均表现出纤维化的全面减轻。我们的数据巩固了MKL1在组织纤维化中所起的关键作用，但指出了MKL1发挥其促纤维化作用的细胞来源。
