{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:20:43Z","timestamp":1777522843120,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["7R01DK129870-03"],"award-info":[{"award-number":["7R01DK129870-03"]}]},{"name":"NIH","award":["PC-151-23"],"award-info":[{"award-number":["PC-151-23"]}]},{"name":"NIH","award":["5R01DK128289-03"],"award-info":[{"award-number":["5R01DK128289-03"]}]},{"name":"NIH","award":["DK119767"],"award-info":[{"award-number":["DK119767"]}]},{"name":"New Jersey Health Foundation","award":["7R01DK129870-03"],"award-info":[{"award-number":["7R01DK129870-03"]}]},{"name":"New Jersey Health Foundation","award":["PC-151-23"],"award-info":[{"award-number":["PC-151-23"]}]},{"name":"New Jersey Health Foundation","award":["5R01DK128289-03"],"award-info":[{"award-number":["5R01DK128289-03"]}]},{"name":"New Jersey Health Foundation","award":["DK119767"],"award-info":[{"award-number":["DK119767"]}]},{"name":"seed grant from the Rutgers NJ Institute for Food Nutrition and Health","award":["7R01DK129870-03"],"award-info":[{"award-number":["7R01DK129870-03"]}]},{"name":"seed grant from the Rutgers NJ Institute for Food Nutrition and Health","award":["PC-151-23"],"award-info":[{"award-number":["PC-151-23"]}]},{"name":"seed grant from the Rutgers NJ Institute for Food Nutrition and Health","award":["5R01DK128289-03"],"award-info":[{"award-number":["5R01DK128289-03"]}]},{"name":"seed grant from the Rutgers NJ Institute for Food Nutrition and Health","award":["DK119767"],"award-info":[{"award-number":["DK119767"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The peptide hormone kisspeptin attenuates liver steatosis, metabolic dysfunction-associated steatohepatitis (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 the 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 b (TGF\u03b2)-the induced expression of fibrogenic and inflammatory markers, in addition to decreasing TGF\u03b2-induced collagen secretion, cell migration, proliferation, and colony formation. Mechanistically, KISS1R signaling downregulated TGF\u03b2 signaling by decreasing SMAD2\/3 phosphorylation via the activation of protein phosphatases, PP2A, which dephosphorylates 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.<\/jats:p>","DOI":"10.3390\/cells13191651","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T03:26:36Z","timestamp":1728012396000},"page":"1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGF\u03b2 Signaling in Hepatic Stellate Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Kavita","family":"Prasad","sequence":"first","affiliation":[{"name":"Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipankar","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shams Gamal Eldin","family":"Shams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3486-630X","authenticated-orcid":false,"given":"Kimberly","family":"Izarraras","sequence":"additional","affiliation":[{"name":"Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent","family":"Mayfield","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-3052","authenticated-orcid":false,"given":"Maryjka B.","family":"Blaszczyk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongren","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-2723","authenticated-orcid":false,"given":"Utpal B.","family":"Pajvani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-6195","authenticated-orcid":false,"given":"Scott L.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9191-9877","authenticated-orcid":false,"given":"Moshmi","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Akkiz, H., Gieseler, R.K., and Canbay, A. 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