| First Author | Pitera JE | Year | 2004 |
| Journal | Am J Pathol | Volume | 165 |
| Issue | 6 | Pages | 1895-906 |
| PubMed ID | 15579434 | Mgi Jnum | J:94974 |
| Mgi Id | MGI:3522390 | Doi | 10.1016/S0002-9440(10)63242-7 |
| Citation | Pitera JE, et al. (2004) Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2-deficient mice. Am J Pathol 165(6):1895-906 |
| abstractText | Angiopoietin-2 (Ang-2) modulates Tie-2 receptor activation. In mouse kidney maturation, Ang-2 is expressed in arteries, with lower levels in tubules, whereas Tie-2 is expressed by endothelia. We hypothesized that Ang-2 deficiency disrupts kidney vessel patterning. The normal renal cortical peritubular space contains fenestrated capillaries, which have few pericytes; they receive water and solutes which proximal tubules reclaim from the glomerular filtrate. In wild-type neonates, alpha smooth muscle actin (alpha SMA), platelet-derived growth factor receptor beta (PDGFR beta), and desmin-expressing cells were not prominent in this compartment. In Ang-2 null mutants, alpha SMA, desmin, and PDGFR beta prominently immunolocalized in cortical peritubular locations. Some alpha SMA-positive cells were closely associated with CD31- and Tie-2-positive peritubular capillary endothelia, and some of the alpha SMA-positive cells expressed PDGFR beta, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like identity. Immunoblotting suggested an increase of total and tyrosine-phosphorylated Tie-2 proteins in null mutant versus wild-type kidneys, and electron microscopy confirmed disorganized capillaries and adjacent cells in cortical peritubular spaces in mutant neonate kidneys. Hence, Ang-2 deficiency causes dysmorphogenesis of cortical peritubular capillaries, with adjacent cells expressing pericyte-like markers; we speculate the latter effect is caused by disturbed paracrine signaling between endothelial and surrounding mesenchymal precursor cells. |
