IHG-1 amplifies TGF-beta1 signaling and is increased in renal fibrosis.
J Am Soc Nephrol
; 19(9): 1672-80, 2008 Sep.
Article
in En
| MEDLINE
| ID: mdl-18508967
ABSTRACT
Induced in high glucose-1 (IHG-1) is an evolutionarily conserved gene transcript upregulated by high extracellular glucose concentrations, but its function is unknown. Here, it is reported that the abundance of IHG-1 mRNA is nearly 10-fold higher in microdissected, tubule-rich renal biopsies from patients with diabetic nephropathy compared with control subjects. In the diabetic nephropathy specimens, in situ hybridization localized IHG-1 to tubular epithelial cells along with TGF-beta1 and activated Smad3, suggesting a possible role in the development of tubulointerstitial fibrosis. Supporting this possibility, IHG-1 mRNA and protein expression also increased with unilateral ureteral obstruction. In the HK-2 proximal tubule cell line, overexpression of IHG-1 increased TGF-beta1-stimulated expression of connective tissue growth factor and fibronectin. IHG-1 was found to amplify TGF-beta1-mediated transcriptional activity by increasing and prolonging phosphorylation of Smad3. Conversely, inhibition of endogenous IHG-1 with small interference RNA suppressed transcriptional responses to TGF-beta1. In summary, IHG-1, which increases in diabetic nephropathy, may enhance the actions of TGF-beta1 and contribute to the development of tubulointerstitial fibrosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ureteral Obstruction
/
Proteins
/
Diabetic Nephropathies
/
Transforming Growth Factor beta1
/
Kidney Tubules
Limits:
Humans
Language:
En
Journal:
J Am Soc Nephrol
Journal subject:
NEFROLOGIA
Year:
2008
Document type:
Article
Affiliation country:
Ireland