Version 1
: Received: 12 September 2024 / Approved: 14 September 2024 / Online: 14 September 2024 (08:48:27 CEST)
How to cite:
Prasad, K.; Bhattacharya, D.; Shams, S. G. E.; Izarraras, K.; Hart, T.; Mayfield, B.; Blaszczyk, M. B.; Zhou, Z.; Pajvani, U. B.; Friedman, S. L.; Bhattacharya, M. Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFb Signaling in Hepatic Stellate Cells. Preprints2024, 2024091111. https://doi.org/10.20944/preprints202409.1111.v1
Prasad, K.; Bhattacharya, D.; Shams, S. G. E.; Izarraras, K.; Hart, T.; Mayfield, B.; Blaszczyk, M. B.; Zhou, Z.; Pajvani, U. B.; Friedman, S. L.; Bhattacharya, M. Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFb Signaling in Hepatic Stellate Cells. Preprints 2024, 2024091111. https://doi.org/10.20944/preprints202409.1111.v1
Prasad, K.; Bhattacharya, D.; Shams, S. G. E.; Izarraras, K.; Hart, T.; Mayfield, B.; Blaszczyk, M. B.; Zhou, Z.; Pajvani, U. B.; Friedman, S. L.; Bhattacharya, M. Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFb Signaling in Hepatic Stellate Cells. Preprints2024, 2024091111. https://doi.org/10.20944/preprints202409.1111.v1
APA Style
Prasad, K., Bhattacharya, D., Shams, S. G. E., Izarraras, K., Hart, T., Mayfield, B., Blaszczyk, M. B., Zhou, Z., Pajvani, U. B., Friedman, S. L., & Bhattacharya, M. (2024). Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFb Signaling in Hepatic Stellate Cells. Preprints. https://doi.org/10.20944/preprints202409.1111.v1
Chicago/Turabian Style
Prasad, K., Scott L. Friedman and Moshmi Bhattacharya. 2024 "Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFb Signaling in Hepatic Stellate Cells" Preprints. https://doi.org/10.20944/preprints202409.1111.v1
Abstract
The peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated stea-tohepatitis (MASH) and fibrosis in mouse models, by signaling via the kisspeptin 1 receptor (KISS1R). However, whether kisspeptin impacts fibrogenesis in the human liver is not known. We investigated the impact of a potent kisspeptin analog (KPA) on fibrogenesis using human precision cut liver slices (hPCLS) from fibrotic livers from male patients, in human hepatic stellate cells (HSCs), LX-2 and in primary mouse HSCs. In hPCLS, 48 h and 72 h of KPA (3 nM, 100 nM) treatment decreased collagen secretion, and lowered expression of fibrogenic and inflammatory markers. Immunohistochemical studies revealed that KISS1R is expressed and localized to HSCs in MASH/fibrotic livers. In HSCs, KPA treatment reduced transforming growth factor beta (TGFb)-induced expression of fibrogenic and inflammatory markers, in addition to decreasing TGFb induced collagen secretion, cell migration, proliferation and colony formation. Mechanistically, KISS1R signaling downregulated TGFb signaling by decreasing SMAD2/3 phosphorylation, via activation of protein-phosphatases PP2A, that dehosphorylates SMAD 2/3. This study revealed for the first time that kisspeptin reverses human hepatic fibrogenesis thus identifying it as a new therapeutic target to treat hepatic fibrosis.
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
