PMID- 18599338
OWN - NLM
STAT- MEDLINE
DCOM- 20081008
LR  - 20161124
IS  - 1357-2725 (Print)
IS  - 1357-2725 (Linking)
VI  - 40
IP  - 11
DP  - 2008
TI  - A new mouse model of Peyronie's disease: an increased expression of 
      hypoxia-inducible factor-1 target genes during the development of penile changes.
PG  - 2638-48
LID - 10.1016/j.biocel.2008.05.012 [doi]
AB  - Peyronie's disease (PD) is characterized by an inflammatory response beneath the 
      tunica albuginea with fibroblast proliferation forming a thickened fibrous plaque 
      that may cause pain, penile curvature and erectile dysfunction. The progression 
      of the PD plaque may eventually lead to calcification or ossification. Current 
      therapeutic success is often unsatisfactory because of limited insight into 
      disease mechanisms. Research has been hampered by the lack of a universally 
      accepted animal model. We describe an animal model of spontaneous PD in tight 
      skin (Tsk) mice, a C57Bl/6J subline that reproduces with age important features 
      of the human disease (fibrous plaque formation, penile bending and areas of 
      chondroid metaplasia with heterotopic ossification). Histological analysis 
      demonstrated an evident structural disorganization of the tunica albuginea with 
      excessive accumulation of type I collagen. At 12 months of age, fibrous plaques 
      with areas of chondroid metaplasia and heterotopic ossification characterized Tsk 
      penises. The up-regulation of hypoxia-inducible factor-1 (HIF-1) leads to an 
      increased downstream expression of HIF-1 target genes, such as TGFbeta and iNOS. 
      These factors, together with some PDGF family members, can cause collagen 
      deposition in Tsk penises. They can also influence chondrocyte differentiation 
      and heterotopic bone formation. In conclusion, hypoxia, HIF-1 and HIF-1 target 
      genes appear to play an important role in the pathogenesis of PD in Tsk mice. 
      This mouse model that is the first example of naturally occurring model of PD in 
      laboratory animals may aid in the identification of signalling pathways crucial 
      for PD and should facilitate the designing and testing of new therapeutic 
      interventions.
FAU - Lucattelli, Monica
AU  - Lucattelli M
AD  - Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanita Pubblica, 
      Universita di Siena, Italy.
FAU - Lunghi, Benedetta
AU  - Lunghi B
FAU - Fineschi, Silvia
AU  - Fineschi S
FAU - Mirone, Vincenzo
AU  - Mirone V
FAU - d'Emmanuele di Villa Bianca, Roberta
AU  - d'Emmanuele di Villa Bianca R
FAU - Longo, Nicola
AU  - Longo N
FAU - Imbimbo, Ciro
AU  - Imbimbo C
FAU - De Palma, Raffaele
AU  - De Palma R
FAU - Sorrentino, Raffaella
AU  - Sorrentino R
FAU - Lungarella, Giuseppe
AU  - Lungarella G
FAU - Cirino, Giuseppe
AU  - Cirino G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080528
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type II)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Collagen Type I/genetics/metabolism
MH  - Collagen Type II/genetics/metabolism
MH  - *Disease Models, Animal
MH  - Female
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - *Penile Induration/genetics/pathology
MH  - Penis/anatomy & histology/*pathology
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2008/07/05 09:00
MHDA- 2008/10/09 09:00
CRDT- 2008/07/05 09:00
PHST- 2008/03/17 00:00 [received]
PHST- 2008/05/05 00:00 [revised]
PHST- 2008/05/14 00:00 [accepted]
PHST- 2008/07/05 09:00 [pubmed]
PHST- 2008/10/09 09:00 [medline]
PHST- 2008/07/05 09:00 [entrez]
AID - S1357-2725(08)00210-0 [pii]
AID - 10.1016/j.biocel.2008.05.012 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2008;40(11):2638-48. doi: 10.1016/j.biocel.2008.05.012. 
      Epub 2008 May 28.