| First Author | Ivey MJ | Year | 2019 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 317 |
| Issue | 2 | Pages | H330-H344 |
| PubMed ID | 31125253 | Mgi Jnum | J:277673 |
| Mgi Id | MGI:6331204 | Doi | 10.1152/ajpheart.00054.2019 |
| Citation | Ivey MJ, et al. (2019) Platelet-derived growth factor receptor-alpha is essential for cardiac fibroblast survival. Am J Physiol Heart Circ Physiol 317(2):H330-H344 |
| abstractText | Platelet-derived growth factor receptor alpha (PDGFRalpha), a receptor tyrosine kinase required for cardiac fibroblast development, is uniquely expressed by fibroblasts in the adult heart. Despite the consensus that PDGFRalpha is expressed in adult cardiac fibroblasts, we know little about its function when these cells are at rest. Here, we demonstrate that loss of PDGFRalpha in cardiac fibroblasts resulted in a rapid reduction of resident fibroblasts. Furthermore, we observe that phosphatidylinositol 3-kinase signaling was required for PDGFRalpha-dependent fibroblast maintenance. Interestingly, this reduced number of fibroblasts was maintained long-term, suggesting that there is no homeostatic mechanism to monitor fibroblast numbers and restore hearts to wild-type levels. Although we did not observe any systolic functional changes in hearts with depleted fibroblasts, the basement membrane and microvasculature of these hearts were perturbed. Through in vitro analyses, we showed that PDGFRalpha signaling inhibition resulted in an increase in fibroblast cell death, and PDGFRalpha stimulation led to increased levels of the cell survival factor activating transcription factor 3. Our data reveal a unique role for PDGFRalpha signaling in fibroblast maintenance and illustrate that a 50% loss in cardiac fibroblasts does not result in lethality.NEW & NOTEWORTHY Platelet-derived growth factor receptor alpha (PDGFRalpha) is required in developing cardiac fibroblasts, but a functional role in adult, quiescent fibroblasts has not been identified. Here, we demonstrate that PDGFRalpha signaling is essential for cardiac fibroblast maintenance and that there are no homeostatic mechanisms to regulate fibroblast numbers in the heart. PDGFR signaling is generally considered mitogenic in fibroblasts, but these data suggest that this receptor may direct different cellular processes depending on the cell's maturation and activation status. |
