title: PIN1 Suppresses the Hepatic Differentiation of Pulp Stem Cells via Wnt3a.
abstract: This study aimed to investigate the role of PIN1 on the hepatic differentiation of human dental pulp stem cells (hDPSCs) and its signaling pathway, as well as the potential therapeutic effects of hDPSC transplantation and PIN1 inhibition on CCl4(carbon tetrachloride)-induced liver fibrosis in mice. The in vitro results showed that hepatic differentiation was suppressed by infection with adenovirus-PIN1 and promoted by PIN1 inhibitor juglone via the downregulation of Wnt3a and β-catenin. Compared with treatment with either hDPSC transplantation or juglone alone, the combination of hDPSCs and juglone into CCl4-injured mice significantly suppressed liver fibrosis and restored serum levels of alanine transaminase, aspartate transaminase, and ammonia. Collectively, the present study shows for the first time that PIN1 inhibition promotes hepatic differentiation of hDPSCs through the Wnt/β-catenin pathway. Furthermore, juglone in combination with hDPSC transplantation effectively treats liver fibrosis, suggesting that hDPSC transplantation with PIN1 inhibition may be a novel therapeutic candidate for the treatment of liver injury.
authors.affiliation: 1 Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: 2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Y A
authors.initials: YA
authors.lastname: Cho
authors.affiliation: 2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.affiliation: 2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.affiliation: 2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: W J
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: 2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: E C
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002252:Carbon Tetrachloride Poisoning; D002454:Cell Differentiation; D003782:Dental Pulp / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D009285:Naphthoquinones / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D060449:Wnt Signaling Pathway; D051176:beta Catenin
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones; D051176:beta Catenin; D006909:Hydroxyproline; C005134:juglone
keywords: NIMA-interacting peptidylprolyl isomerase; Wnt3a; dental pulp; differentiation; hepatocytes; liver fibrosis