{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:45:20Z","timestamp":1770144320925,"version":"3.49.0"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004913","name":"University of Palermo (Italy)","doi-asserted-by":"publisher","award":["FFR 2023"],"award-info":[{"award-number":["FFR 2023"]}],"id":[{"id":"10.13039\/501100004913","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Parathyroid-hormone-related protein (PTHrP) is encoded by the PTHLH gene which, via alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141, and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, mid-region (containing a nuclear\/nucleolar targeting signal), and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation, and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated, or nontumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous, and skin tissues, as well as intestinal, renal, hepatic, pulmonary, and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis-, and diabetes-related changes as diseased states. When reported, the biochemical and\/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination are also briefly described.<\/jats:p>","DOI":"10.3390\/biology12070950","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T01:03:02Z","timestamp":1688346182000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Parathyroid Hormone Related Protein (PTHrP)-Associated Molecular Signatures in Tissue Differentiation and Non-Tumoral Diseases"],"prefix":"10.3390","volume":"12","author":[{"given":"Mariangela","family":"Librizzi","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8075-0642","authenticated-orcid":false,"given":"Flores","family":"Naselli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Abruscato","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-5891","authenticated-orcid":false,"given":"Claudio","family":"Luparello","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-7312","authenticated-orcid":false,"given":"Fabio","family":"Caradonna","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universit\u00e0 di Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3390\/cancers3010396","article-title":"Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life\/Death Decisions by Tumor Cells with Potential Clinical Applications","volume":"3","author":"Luparello","year":"2011","journal-title":"Cancers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.biochi.2013.06.014","article-title":"PTHrP in Differentiating Human Mesenchymal Stem Cells: Transcript Isoform Expression, Promoter Methylation, and Protein Accumulation","volume":"95","author":"Longo","year":"2013","journal-title":"Biochimie"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1111\/bph.14709","article-title":"Multiple actions of parathyroid hormone-related protein in breast cancer bone metastasis","volume":"178","author":"Martin","year":"2021","journal-title":"Br. 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