EXPRESSION OF PARATHYROID HORMONE-RELATED PROTEIN IN THE RAT GLOMERULUS AND TUBULE DURING RECOVERY FROM RENAL ISCHEMIA

Parathyroid hormone-related protein (PTHrP) is widely expressed in nor mal adult and fetal tissues, where it acts in an autocrine/paracrine f ashion, stimulates growth and differentiation, and shares early respon se gene characteristics. Since recovery from renal injury is associate d with release of local growth factors, we examined the expression and localization of PTHrP in normal and ischemic adult rat kidney. Male S prague-Dawley rats underwent complete bilateral renal artery occlusion for 45 min, followed by reperfusion for 15 min, and 2, 6, 24, 48, and 72 h. Renal PTHrP mRNA levels, when compared with sham-operated anima ls, increased twofold after ischemia, and peaked within 6 h after repe rfusion. PTH receptor, beta-actin, and cyclophilin mRNA levels all dec reased after ischemia. PTHrP immunohistochemical staining intensity in creased in proximal tubular cells after ischemia, changing its locatio n from diffusely cytoplasmic to subapical by 24 h after reperfusion. I n addition, PTHrP localized to glomerular epithelial cells (visceral a nd parietal), but not to mesangial cells. PTHrP and PTH stimulated pro liferation two- to threefold in cultured mesangial cells. We conclude that PTHrP mRNA and protein production are upregulated after acute ren al ischemic injury, that PTHrP is present in glomerulus and in both pr oximal and distal tubular cells, and that PTHrP stimulates DNA synthes is in mesangial cells. The precise functions of PTHrP in normal and in jured kidney remain to be defined.