Interleukin-driven insulin-like growth factor promotes prostatic inflammatory hyperplasia.
J Pharmacol Exp Ther
; 351(3): 605-15, 2014 Dec.
Article
in En
| MEDLINE
| ID: mdl-25292180
ABSTRACT
Prostatic inflammation is of considerable importance to urologic research because of its association with benign prostatic hyperplasia and prostate cancer. However, the mechanisms by which inflammation leads to proliferation and growth remain obscure. Here, we show that insulin-like growth factors (IGFs), previously known as critical developmental growth factors during prostate organogenesis, are induced by inflammation as part of the proliferative recovery to inflammation. Using genetic models and in vivo IGF receptor blockade, we demonstrate that the hyperplastic response to inflammation depends on interleukin-1-driven IGF signaling. We show that human prostatic hyperplasia is associated with IGF pathway activation specifically localized to foci of inflammation. This demonstrates that mechanisms of inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors, further establishing a link between inflammatory and developmental signals and providing a mechanistic basis for the management of proliferative diseases by IGF pathway modulation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Hyperplasia
/
Somatomedins
/
Interleukin-1
Type of study:
Prognostic_studies
Limits:
Aged
/
Animals
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Pharmacol Exp Ther
Year:
2014
Document type:
Article