Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium
Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in sev...
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2023-10-01
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| Series: | European Journal of Histochemistry |
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| Online Access: | https://www.ejh.it/index.php/ejh/article/view/3846 |
| _version_ | 1797655628935593984 |
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| author | Arianna Casini Giorgio Vivacqua Rosa Vaccaro Anastasia Renzi Stefano Leone Luigi Pannarale Antonio Franchitto Paolo Onori Romina Mancinelli Eugenio Gaudio |
| author_facet | Arianna Casini Giorgio Vivacqua Rosa Vaccaro Anastasia Renzi Stefano Leone Luigi Pannarale Antonio Franchitto Paolo Onori Romina Mancinelli Eugenio Gaudio |
| author_sort | Arianna Casini |
| collection | DOAJ |
| description |
Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.
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| first_indexed | 2024-03-11T17:17:15Z |
| format | Article |
| id | doaj.art-2c43b6b0ed194af7baa701fac217cad6 |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-03-11T17:17:15Z |
| publishDate | 2023-10-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-2c43b6b0ed194af7baa701fac217cad62023-10-19T20:27:40ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062023-10-0167410.4081/ejh.2023.3846Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epitheliumArianna Casini0Giorgio Vivacqua1Rosa Vaccaro2Anastasia Renzi3Stefano Leone4Luigi Pannarale5Antonio Franchitto6Paolo Onori7Romina Mancinelli8Eugenio Gaudio9Department of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeIntegrated Research Center (PRAAB), Campus Biomedico University of RomeDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeDepartment of Pathology, Akershus University Hospital, LorenskogDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeDepartment of Movement, Human and Health Sciences, University of Rome Foro ItalicoDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of RomeDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF. https://www.ejh.it/index.php/ejh/article/view/3846Liverbiliary epitheliumcholangiocyte proliferationcocaine-amphetamine regulated transcript (CART) |
| spellingShingle | Arianna Casini Giorgio Vivacqua Rosa Vaccaro Anastasia Renzi Stefano Leone Luigi Pannarale Antonio Franchitto Paolo Onori Romina Mancinelli Eugenio Gaudio Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium European Journal of Histochemistry Liver biliary epithelium cholangiocyte proliferation cocaine-amphetamine regulated transcript (CART) |
| title | Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium |
| title_full | Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium |
| title_fullStr | Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium |
| title_full_unstemmed | Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium |
| title_short | Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium |
| title_sort | expression and role of cocaine amphetamine regulated transcript cart in the proliferation of biliary epithelium |
| topic | Liver biliary epithelium cholangiocyte proliferation cocaine-amphetamine regulated transcript (CART) |
| url | https://www.ejh.it/index.php/ejh/article/view/3846 |
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