Pioneering PGC-1α-boosted secretome : a novel approach to combating liver fibrosis
Copyright © 2024, the Korean Surgical Society..
Purpose: Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis.
Methods: Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models.
Results: In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker).
Conclusion: These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
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| Enthalten in: |
Annals of surgical treatment and research - 106(2024), 3 vom: 01. März, Seite 155-168 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Seo, Chang Ho [VerfasserIn] |
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| Links: |
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| Themen: |
Adipose-derived stem cells |
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| Anmerkungen: |
Date Revised 05.03.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.4174/astr.2024.106.3.155 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369253655 |
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| 245 | 1 | 0 | |a Pioneering PGC-1α-boosted secretome |b a novel approach to combating liver fibrosis |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2024, the Korean Surgical Society. | ||
| 520 | |a Purpose: Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis | ||
| 520 | |a Methods: Upon achieving a cellular confluence of 70%-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models | ||
| 520 | |a Results: In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec-treated group, along with reduced collagen type 1A expression (a profibrogenic marker) | ||
| 520 | |a Conclusion: These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adipose-derived stem cells | |
| 650 | 4 | |a Liver fibrosis | |
| 650 | 4 | |a Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha | |
| 650 | 4 | |a Secretome | |
| 700 | 1 | |a Na, Gun Hyung |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Dosang |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jung Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Tae Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Ok-Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sang Chul |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kee-Hwan |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Ho Joong |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Say-June |e verfasserin |4 aut | |
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