Phosphodiesterase 5a Signalling in Skeletal Muscle Pathophysiology.

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 isoforms in cardiomyocytes, and we have found that the expression of specific 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 isoforms in the pathophysiology of skeletal muscle. We found that skeletal muscle tissues and myogenic cells express and isoforms, and we observed an increased expression of in damaged skeletal muscles, while levels remained unchanged. We also cloned and characterized the promoters that control the transcription of isoforms, investigating which of the transcription factors predicted by bioinformatics analysis could be involved in their modulation. In conclusion, we found an overexpression of in compromised muscle and identified an involvement of MyoD and Runx1 in transcriptional activity.