Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia. J Clin Invest 1993 Dec;92(6):2850-7
Date
12/01/1993Pubmed ID
8254039Pubmed Central ID
PMC288486DOI
10.1172/JCI116905Scopus ID
2-s2.0-0027133219 (requires institutional sign-in at Scopus site) 72 CitationsAbstract
Parathyroid hormone-related protein (PTHrP) is widely expressed in normal adult and fetal tissues, where it acts in an autocrine/paracrine fashion, stimulates growth and differentiation, and shares early response gene characteristics. Since recovery from renal injury is associated with release of local growth factors, we examined the expression and localization of PTHrP in normal and ischemic adult rat kidney. Male Sprague-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 animals, increased twofold after ischemia, and peaked within 6 h after reperfusion. PTH receptor, beta-actin, and cyclophilin mRNA levels all decreased after ischemia. PTHrP immunohistochemical staining intensity increased in proximal tubular cells after ischemia, changing its location from diffusely cytoplasmic to subapical by 24 h after reperfusion. In addition, PTHrP localized to glomerular epithelial cells (visceral and parietal), but not to mesangial cells. PTHrP and PTH stimulated proliferation two- to threefold in cultured mesangial cells. We conclude that PTHrP mRNA and protein production are upregulated after acute renal ischemic injury, that PTHrP is present in glomerulus and in both proximal and distal tubular cells, and that PTHrP stimulates DNA synthesis in mesangial cells. The precise functions of PTHrP in normal and injured kidney remain to be defined.
Author List
Soifer NE, Van Why SK, Ganz MB, Kashgarian M, Siegel NJ, Stewart AFAuthor
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAmino Acid Isomerases
Animals
Blotting, Northern
Carrier Proteins
Gene Expression
Immunohistochemistry
Ischemia
Kidney
Kidney Glomerulus
Kidney Tubules
Male
Parathyroid Hormone-Related Protein
Peptidylprolyl Isomerase
Protein Biosynthesis
Proteins
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Parathyroid Hormone
Reference Values
Renal Artery
Reperfusion