Pioneering PGC-1αα–boosted secretome: a novel approach to combating liver fibrosis
10.4174/astr.2024.106.3.155
- Author:
Chang Ho SEO
1
;
Gun Hyung NA
;
Dosang LEE
;
Jung Hyun PARK
;
Tae Ho HONG
;
Ok-Hee KIM
;
Sang Chul LEE
;
Kee-Hwan KIM
;
Ho Joong CHOI
;
Say-June KIM
Author Information
1. Department of Surgery, Bucheon St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea
- Publication Type:ORIGINAL ARTICLE
- From:Annals of Surgical Treatment and Research
2024;106(3):155-168
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
