{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:16:35Z","timestamp":1789139795830,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University","award":["RP120172A796BA45"],"award-info":[{"award-number":["RP120172A796BA45"]}]},{"name":"Sapienza University","award":["RM12117A5C8B2B1A"],"award-info":[{"award-number":["RM12117A5C8B2B1A"]}]},{"name":"Sapienza University","award":["RM120172A3B45898"],"award-info":[{"award-number":["RM120172A3B45898"]}]},{"name":"Sapienza University","award":["000315-19"],"award-info":[{"award-number":["000315-19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphodiesterase 5A (PDE5A) is involved in cGMP hydrolysis, regulating many physiological processes. Increased activity of PDE5A has been found in several pathological conditions, and the pharmacological inhibition of PDE5 has been demonstrated to have several therapeutic applications. We have identified the presence of three different Pde5a isoforms in cardiomyocytes, and we have found that the expression of specific Pde5a isoforms may have a causal role in the onset of pathological responses in these cells. In our previous study, we demonstrated that PDE5A inhibition could ameliorate muscular dystrophy by acting at different levels, as assessed by the altered genomic response of muscular cells following treatment with the PDE5A inhibitor tadalafil. Thus, considering the importance of PDE5A in various pathophysiological conditions, we further investigated the regulation of this enzyme. Here, we analysed the expression of Pde5a isoforms in the pathophysiology of skeletal muscle. We found that skeletal muscle tissues and myogenic cells express Pde5a1 and Pde5a2 isoforms, and we observed an increased expression of Pde5a1 in damaged skeletal muscles, while Pde5a2 levels remained unchanged. We also cloned and characterized the promoters that control the transcription of Pde5a isoforms, investigating which of the transcription factors predicted by bioinformatics analysis could be involved in their modulation. In conclusion, we found an overexpression of Pde5a1 in compromised muscle and identified an involvement of MyoD and Runx1 in Pde5a1 transcriptional activity.<\/jats:p>","DOI":"10.3390\/ijms24010703","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Phosphodiesterase 5a Signalling in Skeletal Muscle Pathophysiology"],"prefix":"10.3390","volume":"24","author":[{"given":"Valeria","family":"De Arcangelis","sequence":"first","affiliation":[{"name":"Neurology Unit Department of Neuroscience, Fondazione Policlinico Univeristario Agostino Gemelli IRCC, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Barbagallo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, \u201cKore\u201d University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-874X","authenticated-orcid":false,"given":"Federica","family":"Campolo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Gabriela","family":"de Oliveira do Rego","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cC. Darwin\u201d, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6387-5187","authenticated-orcid":false,"given":"Manuela","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, IBBC-CNR, 00015 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0572-5900","authenticated-orcid":false,"given":"Fabio","family":"Naro","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cC. Darwin\u201d, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Monaco","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1152\/japplphysiol.00634.2017","article-title":"Exercise training improves blood flow to contracting skeletal muscle of older men via enhanced cGMP signalling","volume":"124","author":"Piil","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1152\/physrev.00022.2015","article-title":"Molecular Physiology of Membrane Guanylyl Cyclase Receptors","volume":"96","author":"Kuhn","year":"2016","journal-title":"Physiol. 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