JOURNAL OF INTERFERON & CYTOKINE RESEARCH

Interstitial fi brosis 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 pos-sible correlation between OSM level and kidney tissue fi brosis. Indeed, unilateral ureteral obstruction (UUO), a model of renal fi brosis, 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 epi-thelial-myofi broblast transdifferentiation. cDNA microarray technology identifi ed 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 fi broblasts. In vivo, treat-ment 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 fi brogenesis, possibly by inducing myofi broblast transdifferentiation of TECs as well as leukocyte infi ltration. This process may, in turn, contribute in part to progression of obstructive nephropathy and makes OSM a promising therapeutic target in renal fi brosis