Faculty Collaboration Database

Early differential expression of oncostatin M in obstructive nephropathy. J Interferon Cytokine Res 2010 Jul;30(7):513-23

Date

07/16/2010

Pubmed ID

20626292

Pubmed Central ID

PMC2950062

DOI

10.1089/jir.2009.0105

Scopus ID

2-s2.0-77954890325 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Interstitial fibrosis plays a major role in progression of renal diseases. Oncostatin M (OSM) is a cytokine that regulates cell survival, differentiation, and proliferation. Renal tissue from patients with chronic obstructive nephropathy was examined for OSM expression. The elevated levels in diseased human kidneys suggested possible correlation between OSM level and kidney tissue fibrosis. Indeed, unilateral ureteral obstruction (UUO), a model of renal fibrosis, increased OSM and OSM receptor (OSM-R) expression in a time-dependent manner within hours following UUO. In vitro, OSM overexpression in tubular epithelial cells (TECs) resulted in epithelial-myofibroblast transdifferentiation. cDNA microarray technology identified up-regulated expression of immune modulators in obstructed compared with sham-operated kidneys. In vitro, OSM treatment up-regulated CC chemokine ligand CCL7, and CXC chemokine ligand (CXCL)-14 mRNA in kidney fibroblasts. In vivo, treatment of UUO mice with neutralizing anti-OSM antibody decreased renal chemokines expression. In conclusion, OSM is up-regulated in kidney tissue early after urinary obstruction. Therefore, OSM might play an important role in initiation of renal fibrogenesis, possibly by inducing myofibroblast transdifferentiation of TECs as well as leukocyte infiltration. This process may, in turn, contribute in part to progression of obstructive nephropathy and makes OSM a promising therapeutic target in renal fibrosis.

Author List

Elbjeirami WM, Truong LD, Tawil A, Wang W, Dawson S, Lan HY, Zhang P, Garcia GE, Wayne Smith C

Author

Sara K. Dawson MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Blocking
Cell Transdifferentiation
Cells, Cultured
Chemokines
Epithelial Cells
Fibrosis
Gene Expression Profiling
Humans
Kidney Tubules
Male
Mice
Mice, Inbred C57BL
Myofibroblasts
Oligonucleotide Array Sequence Analysis
Oncostatin M
Rats
Rats, Sprague-Dawley
Receptors, Oncostatin M
Ureteral Obstruction