| First Author | Cuevas RA | Year | 2023 |
| Journal | Am J Physiol Cell Physiol | Volume | 324 |
| Issue | 2 | Pages | C327-C338 |
| PubMed ID | 36503240 | Mgi Jnum | J:347696 |
| Mgi Id | MGI:7435134 | Doi | 10.1152/ajpcell.00054.2022 |
| Citation | Cuevas RA, et al. (2023) Ecto-5'-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFbeta-2 induced elastin and cellular contraction. Am J Physiol Cell Physiol 324(2):C327-C338 |
| abstractText | Arterial calcification due to deficiency of CD73 (ACDC) is a rare genetic disease caused by a loss-of-function mutation in the NT5E gene encoding the ecto-5'-nucleotidase (cluster of differentiation 73, CD73) enzyme. Patients with ACDC develop vessel arteriomegaly, tortuosity, and vascular calcification in their lower extremity arteries. Histological analysis shows that patients with ACDC vessels exhibit fragmented elastin fibers similar to that seen in aneurysmal-like pathologies. It is known that alterations in transforming growth factor beta (TGFbeta) pathway signaling contribute to this elastin phenotype in several connective tissue diseases, as TGFbeta regulates extracellular matrix (ECM) remodeling. Our study investigates whether CD73-derived adenosine modifies TGFbeta signaling in vascular smooth muscle cells (SMCs). We show that Nt5e(-/-) SMCs have elevated contractile markers and elastin gene expression compared with Nt5e(+/+) SMCs. Ecto-5'-nucleotidase (Nt5e)-deficient SMCs exhibit increased TGFbeta-2 and activation of small mothers against decapentaplegic (SMAD) signaling, elevated elastin transcript and protein, and potentiate SMC contraction. These effects were diminished when the A2b adenosine receptor was activated. Our results identify a novel link between adenosine and TGFbeta signaling, where adenosine signaling via the A2b adenosine receptor attenuates TGFbeta signaling to regulate SMC homeostasis. We discuss how disruption in adenosine signaling is implicated in ACDC vessel tortuosity and could potentially contribute to other aneurysmal pathogenesis. |
