RGD Reference Report - Progesterone modulates integrin {alpha}2 (ITGA2) and {alpha}11 (ITGA11) in the pregnant cervix. - Rat Genome Database

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Progesterone modulates integrin {alpha}2 (ITGA2) and {alpha}11 (ITGA11) in the pregnant cervix.

Authors: Ji, H  Long, V  Briody, V  Chien, EK 
Citation: Ji H, etal., Reprod Sci. 2011 Feb;18(2):156-63. doi: 10.1177/1933719110382305. Epub 2010 Oct 19.
RGD ID: 8693208
Pubmed: PMID:20959644   (View Abstract at PubMed)
DOI: DOI:10.1177/1933719110382305   (Journal Full-text)

OBJECTIVE: Fibrillar collagen in the cervical extracellular matrix (ECM) is the predominant component providing mechanical support. Cellular integrins contribute to structural integrity by cross-linking ECM components. We investigated the expression of collagen-binding integrins in the normal rat gestation and after treatment with mifepristone to determine whether integrin modulation is involved in changes in tissue resistance. STUDY DESIGN: Cervical tissue was harvested from nonpregnant and timed pregnant Sprague-Dawley rats. Normal gestational expression was evaluated in nonpregnant and timed pregnant tissue on days 12, 16, 18, 20, 21 and 22. Progesterone inhibition was induced with 3 mg mifepristone administered on day 15. Primary rat cervical stromal (RCS) cell cultures were generated from nonpregnant rats using tissue explants. The effects of progesterone environment on RCS cells were evaluated in the presence and absence of various inhibitors. Protein expression and signaling pathways were evaluated by Western blot. RESULTS: Integrin alpha2 (ITGA2) expression increased over gestation, peaking at the end of gestation (analysis of variance [ANOVA] P < .01). Integrin alpha11 (ITGA11) expression increased through mid-gestation, peaking on day 18 and decreasing through day 22 (ANOVA P < .001). Progesterone increased the expression of ITGA11 and phosphorylated focal adhesion kinase ([pFAK] P < .002). Mifepristone blocked these effects in vitro. Mifepristone increased ITGA2 and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) in vivo and in vitro. Mifepristone-induced upregulation of ITGA2 was abrogated by inhibition of ERK1/2. CONCLUSION: Progesterone/progesterone withdrawal is involved in regulating the expression of collagen-binding integrins. These changes differ among the collagen-binding integrins. Mitogen-activated protein kinase (MAPK) signaling is involved in regulating some of these integrins.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to organic cyclic compound  IEP 8693208mifeprisoneRGD 
female pregnancy  IEP 8693208 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Itga2  (integrin subunit alpha 2)


Additional Information