Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Pioneering PGC-1α-Boosted Secretome: A Novel Approach to Combating Liver Fibrosis

Version 1 : Received: 1 June 2023 / Approved: 2 June 2023 / Online: 2 June 2023 (03:49:55 CEST)

How to cite: Seo, C.H.; Na, G.H.; Lee, D.; Park, J.H.; Hong, T.H.; Kim, O.; Lee, S.C.; Kim, K.; Choi, H.J.; Kim, S. Pioneering PGC-1α-Boosted Secretome: A Novel Approach to Combating Liver Fibrosis. Preprints 2023, 2023060120. https://doi.org/10.20944/preprints202306.0120.v1 Seo, C.H.; Na, G.H.; Lee, D.; Park, J.H.; Hong, T.H.; Kim, O.; Lee, S.C.; Kim, K.; Choi, H.J.; Kim, S. Pioneering PGC-1α-Boosted Secretome: A Novel Approach to Combating Liver Fibrosis. Preprints 2023, 2023060120. https://doi.org/10.20944/preprints202306.0120.v1

Abstract

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from PGC-1α-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. 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 vivo mouse models. In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to control-secretome (Ctrl-Sec). In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum pro-inflammatory 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, OPA1 (a mitochondrial function marker), and PPARα (an anti-fibrogenic marker) in the PGC-Sec-treated group, along with reduced Collagen 1A expression (a pro-fibrogenic marker). 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.

Keywords

Adipose-derived stem cells (ASCs); Liver fibrosis; Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α); Secretome

Subject

Biology and Life Sciences, Biology and Biotechnology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.