NFATc1 expression in the developing heart valves is responsive to the RANKL pathway and is required for endocardial expression of cathepsin K

Autor: Alexander W. Lange, Katherine E. Yutzey
Rok vydání: 2006
Předmět:
Male
Cathepsin K
NFATc1
Mice
0302 clinical medicine
Fluorescent Antibody Technique
Indirect
In Situ Hybridization
Mice
Knockout
Regulation of gene expression
0303 health sciences
Membrane Glycoproteins
Receptor Activator of Nuclear Factor-kappa B
integumentary system
Embryonic heart
Reverse Transcriptase Polymerase Chain Reaction
Homozygote
RANKL
Gene Expression Regulation
Developmental
Heart Valves
Immunohistochemistry
Cell biology
medicine.anatomical_structure
Female
Signal transduction
musculoskeletal diseases
Heterozygote
medicine.medical_specialty
Mice
Transgenic
Biology
03 medical and health sciences
Organ Culture Techniques
Osteoclast
Internal medicine
medicine
Animals
Heart valve
Molecular Biology
Crosses
Genetic
030304 developmental biology
NFATC Transcription Factors
RANK Ligand
Cell Biology
Cathepsins
Endocrinology
biology.protein
Carrier Proteins
030217 neurology & neurosurgery
Endocardium
Developmental Biology
Zdroj: Developmental Biology. 292:407-417
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2006.01.017
Popis: NFATc1 is necessary for remodeling endocardial cushions into mature heart valve leaflets and is also an essential effector of receptor activator of NFκB ligand (RANKL) signaling required for transcriptional activation of bone matrix remodeling enzymes during osteoclast differentiation. Therefore, developing heart valves were examined to determine if NFATc1 functions in the RANKL pathway during leaflet remodeling. Key components of RANKL signal transduction including RANKL, its receptor RANK, and the downstream remodeling enzyme cathepsin K (Ctsk) are expressed in the heart during valve remodeling and colocalize with NFATc1 in developing valve endocardium. However, the absence of tartrate-resistant acid phosphatase (TRAP) activity and the lack of F4/80-positive macrophage lineage contribution to the remodeling valves demonstrate that certain aspects of osteoclast RANKL function are not shared during valve formation. Analysis of NFATc1−/− mouse embryos shows that NFATc1 is specifically required for endocardial expression of RANKL and Ctsk during valve formation. In addition, RANKL treatment augments expression of NFATc1 and Ctsk in embryonic heart cultures, and the RANKL-mediated increase in Ctsk expression is dependent on NFATc1. Together, these results support a role for RANKL signaling during heart valve development and suggest that valve leaflet morphogenesis involves NFATc1-dependent expression of remodeling enzymes including Ctsk.
Databáze: OpenAIRE
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