Fernandez-Canadas Inmaculada, Badajoz Alejandro, Jimenez-Gonzalez Jesús, Wirenfeldt Martin, Paniagua-Torija Beatriz, Bravo-Jimenez Clara, Del Cerro Mar, Arevalo-Martin Angel, Garcia-Ovejero Daniel
Laboratorio de Neuroinflamacion i2-06, Hospital Nacional de Paraplejicos, Finca La Peraleda s/n, Toledo, 45071, Spain.
Department of Pathology, University Hospital of Southern Denmark, Esbjerg, DK-6000, Denmark.
Sci Rep. 2025 Jan 22;15(1):2826. doi: 10.1038/s41598-025-87131-3.
Spinal cord injury (SCI) causes abnormal liver function, the development of metabolic dysfunction-associated steatotic liver disease features and metabolic impairment in patients. Experimental models also demonstrate acute and chronic changes in the liver that may, in turn, affect SCI recovery. These changes have collectively been proposed to contribute to the development of a SCI-induced metabolic dysfunction-associated steatohepatitis (MASH). However, none of the existent studies have focused on hepatic stellate cells (HSCs), liver resident cells that are the primary drivers of collagen deposition and fibrosis following sustained liver damage. Here, we describe the transient activation of HSCs after a thoracic contusion in rats, considered a clinically relevant model of experimental SCI. We studied HSC during the time course of SCI, from 1 to 45 days post injury. We found a transient activation of HSCs after SCI, beginning with the acute downregulation of Glial Fibrillar Acidic Protein 1dpi. This is followed by a morphological and phenotypical transformation into alpha-smooth muscle actin (ACTA2/SMA) immunoreactive myofibroblast-like cells, peaking at 14 days post-injury and returning to control-like levels at later timepoints (45 days post-injury). These changes are not accompanied by fibrosis development but collagen deposition in peri-portal areas is observed at 45 days.
脊髓损伤（SCI）会导致患者肝功能异常、出现代谢功能障碍相关脂肪性肝病特征及代谢损害。实验模型也显示肝脏会发生急性和慢性变化，而这些变化反过来可能会影响SCI的恢复。这些变化共同被认为促成了SCI诱导的代谢功能障碍相关脂肪性肝炎（MASH）的发生。然而，现有的研究均未聚焦于肝星状细胞（HSCs），肝星状细胞是肝脏驻留细胞，是持续性肝损伤后胶原沉积和纤维化的主要驱动因素。在此，我们描述了大鼠胸段挫伤后肝星状细胞的短暂激活，胸段挫伤被视为实验性SCI的临床相关模型。我们在SCI后的1至45天时间内研究了肝星状细胞。我们发现SCI后肝星状细胞会短暂激活，始于损伤后1天胶质纤维酸性蛋白的急性下调。随后会发生形态和表型转变，成为α-平滑肌肌动蛋白（ACTA2/SMA）免疫反应性肌成纤维细胞样细胞，在损伤后14天达到峰值，并在随后的时间点（损伤后45天）恢复到类似对照的水平。这些变化并未伴随纤维化的发展，但在损伤后45天观察到门静脉周围区域有胶原沉积。
