| First Author | Rodriguez A | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 6 | Pages | 2132-46 |
| PubMed ID | 23570836 | Mgi Jnum | J:197370 |
| Mgi Id | MGI:5492226 | Doi | 10.1016/j.ajpath.2013.01.054 |
| Citation | Rodriguez A, et al. (2013) Phenotypical Differences in Connective Tissue Cells Emerging from Microvascular Pericytes in Response to Overexpression of PDGF-B and TGF-beta1 in Normal Skin in Vivo. Am J Pathol 182(6):2132-46 |
| abstractText | Fibrosis is a deleterious consequence of chronic inflammation in a number of human pathologies ultimately leading to organ dysfunction and failure. Two growth factors that are important in blood vessel physiology and tissue fibrosis, platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta1, were investigated. Adenoviral vectors were used to induce transient overexpression of these growth factors in mouse skin. Changes in tissue structure and protein and mRNA expressions were investigated. Both PDGF-B and TGF-beta1 could initiate but neither could sustain angiogenesis. Instead, vascular regression was observed. Overexpression of both TGF-beta1 and PDGF-B led to a marked macrophage influx and an expansion of the connective tissue cell population. Over time, this effect was sustained in mice treated with TGF-beta1, whereas it was partially reversible in mice treated with PDGF-B. On the basis of structure and expression of phenotypical markers, the emerging connective tissue cell population may originate from microvascular pericytes. TGF-beta1 induced expansion of connective tissue cells with a myofibroblast phenotype, whereas PDGF-B induced a fibroblast phenotype negative for alpha-smooth muscle actin. TGF-beta1 and PDGF-B overexpressions mediated distinct effects on mRNA transcript levels of fibrillar procollagens, their modifying enzymes, small leucin-rich repeat proteoglycans, and matricellular proteins affecting both the composition and the quantity of the extracellular matrix. This study offers new insight into the effects of PDGF-B and TGF-beta1 on the vasculature and connective tissue in vivo. |
