Spinal cord injury induces transient activation of hepatic stellate cells in rat liver
Abstract 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 recov...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87131-3 |
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| author | Inmaculada Fernandez-Canadas Alejandro Badajoz Jesús Jimenez-Gonzalez Martin Wirenfeldt Beatriz Paniagua-Torija Clara Bravo-Jimenez Mar Del Cerro Angel Arevalo-Martin Daniel Garcia-Ovejero |
| author_facet | Inmaculada Fernandez-Canadas Alejandro Badajoz Jesús Jimenez-Gonzalez Martin Wirenfeldt Beatriz Paniagua-Torija Clara Bravo-Jimenez Mar Del Cerro Angel Arevalo-Martin Daniel Garcia-Ovejero |
| author_sort | Inmaculada Fernandez-Canadas |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-7ad547d4cb75444fbca2d414a1f91906 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-7ad547d4cb75444fbca2d414a1f919062025-01-26T12:23:44ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-87131-3Spinal cord injury induces transient activation of hepatic stellate cells in rat liverInmaculada Fernandez-Canadas0Alejandro Badajoz1Jesús Jimenez-Gonzalez2Martin Wirenfeldt3Beatriz Paniagua-Torija4Clara Bravo-Jimenez5Mar Del Cerro6Angel Arevalo-Martin7Daniel Garcia-Ovejero8Laboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosDepartment of Pathology, University Hospital of Southern DenmarkLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosLaboratorio de Neuroinflamacion i2-06, Hospital Nacional de ParaplejicosAbstract 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.https://doi.org/10.1038/s41598-025-87131-3GFAPHepatic stellate cellsFibrosisSpinal cordLiverSMA |
| spellingShingle | Inmaculada Fernandez-Canadas Alejandro Badajoz Jesús Jimenez-Gonzalez Martin Wirenfeldt Beatriz Paniagua-Torija Clara Bravo-Jimenez Mar Del Cerro Angel Arevalo-Martin Daniel Garcia-Ovejero Spinal cord injury induces transient activation of hepatic stellate cells in rat liver Scientific Reports GFAP Hepatic stellate cells Fibrosis Spinal cord Liver SMA |
| title | Spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| title_full | Spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| title_fullStr | Spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| title_full_unstemmed | Spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| title_short | Spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| title_sort | spinal cord injury induces transient activation of hepatic stellate cells in rat liver |
| topic | GFAP Hepatic stellate cells Fibrosis Spinal cord Liver SMA |
| url | https://doi.org/10.1038/s41598-025-87131-3 |
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