Gene interactions and pathways from curated databases and text-mining
In Vitro Cell Dev Biol Anim 2006, PMID: 16848631

Matrix metalloproteinase-7 and epidermal growth factor receptor mediate hypoxia-induced extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activation and subsequent proliferation in bladder smooth muscle cells.

Sabha, Nesrin; Aitken, Karen; Lorenzo, Armando J; Szybowska, Marta; Jairath, Ashish; Bägli, Darius J

Low oxygen tension (hypoxia) has been implicated in proliferation of vascular smooth muscle cells (SMCs) of the lung. Tissue hypoxia also occurs in the obstructed bladder. The extracellular-regulated kinase mitogen-activated protein kinase 1/2 (Erk1/2) pathway is induced in many cell types during hypoxia. We examined whether hypoxia (3% O2), compared with normoxia (21% O2), induces proliferation responses and activation of the Erk1/2 pathways in primary rat bladder smooth muscle cells (BSMCs). We show that hypoxia induces proliferation of BSMCs at 18 h and, although reduced at 22 h, still remained above normoxic levels. Hypoxia induced a strikingly transient activation of Erk1/2 that lasted only 10-30 min. However, inhibition of the transient Erk1/2 activity with a specific mitogen-activated protein kinase kinase 1 (MEK-1) inhibitor PD 98059 prevented subsequent hypoxia-induced proliferation at 18 h. Interestingly, inhibition of general matrix metalloproteinase (MMP) activity, using either doxycycline or GM 6001, prevented both transient Erk1/2 activity and subsequent proliferation in response to hypoxia. Furthermore, MMP-7 (matrilysin) is activated in the conditioned medium (CM) of BSMCs at 10-20 min of hypoxia. In addition, MMP-7 was also transcriptionally induced at 6 h of hypoxia in an Erk1/2-dependent manner. Moreover, transient Erk1/2 activation and BSMC proliferation were both dependent on epidermal growth factor receptor (EGFR/HER1) but not neu receptor (HER2/ERB2) autophosphorylation. We conclude that hypoxia leads to Erk1/2 activation, which appears to modulate BSMC proliferation through MMP-7-and EGFR-mediated mechanisms.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

mitogen activated protein kinase → epidermal growth factor receptor: " Matrix metalloproteinase-7 and epidermal growth factor receptor mediate hypoxia induced extracellular signal regulated kinase 1/2 mitogen activated protein kinase activation and subsequent proliferation in bladder smooth muscle cells "

mitogen activated protein kinase → Matrix metalloproteinase-7: " Matrix metalloproteinase-7 and epidermal growth factor receptor mediate hypoxia induced extracellular signal regulated kinase 1/2 mitogen activated protein kinase activation and subsequent proliferation in bladder smooth muscle cells "

Erk1/2 → matrix metalloproteinase ( MMP ): " However, inhibition of the transient Erk1/2 activity with a specific mitogen activated protein kinase kinase 1 ( MEK-1 ) inhibitor PD 98059 prevented subsequent hypoxia induced proliferation at 18 h. Interestingly, inhibition of general matrix metalloproteinase ( MMP ) activity, using either doxycycline or GM 6001, prevented both transient Erk1/2 activity and subsequent proliferation in response to hypoxia "

Erk1/2 → matrix metalloproteinase ( MMP ): " However, inhibition of the transient Erk1/2 activity with a specific mitogen activated protein kinase kinase 1 ( MEK-1 ) inhibitor PD 98059 prevented subsequent hypoxia induced proliferation at 18 h. Interestingly, inhibition of general matrix metalloproteinase ( MMP ) activity, using either doxycycline or GM 6001, prevented both transient Erk1/2 activity and subsequent proliferation in response to hypoxia "

MMP-7 — Erk1/2: " In addition, MMP-7 was also transcriptionally induced at 6 h of hypoxia in an Erk1/2 dependent manner "

MMP-7 — Erk1/2: " In addition, MMP-7 was also transcriptionally induced at 6 h of hypoxia in an Erk1/2 dependent manner "

MMP-7 — Erk1/2: " In addition, MMP-7 was also transcriptionally induced at 6 h of hypoxia in an Erk1/2 dependent manner "

Erk1/2 → epidermal growth factor receptor: " Moreover, transient Erk1/2 activation and BSMC proliferation were both dependent on epidermal growth factor receptor ( EGFR/HER1 ) but not neu receptor ( HER2/ERB2 ) autophosphorylation "

Erk1/2 → epidermal growth factor receptor: " Moreover, transient Erk1/2 activation and BSMC proliferation were both dependent on epidermal growth factor receptor ( EGFR/HER1 ) but not neu receptor ( HER2/ERB2 ) autophosphorylation "

Manually curated Databases

No curated data.