Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19+ B lymphocytes in the peripheral blood.
Int J Hematol
; 105(6): 748-757, 2017 Jun.
Article
en En
| MEDLINE
| ID: mdl-28299632
ABSTRACT
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-ß-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles. Transgenic overexpression of kallistatin suppressed Wnt-TCF/LEF-ß-catenin signaling in bone marrow, as demonstrated using a Wnt reporter mouse. Further, kallistatin overexpression and treatment were associated with reduced Wnt-TCF/LEF-ß-catenin activity in CD34+ c-kit+ bone marrow cells and CD19+ B lymphocytes, with reduced levels of these populations in bone marrow and peripheral circulation, respectively. The presence of CD3+CD4+, CD3+CD8+, and CD3- NK1.1+ T lymphocytes were not significantly affected. Our data suggest that overexpression of kallistatin interferes with lymphopoiesis, ultimately impacting the level of circulating CD19+ B lymphocytes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Serpinas
/
Antígenos CD19
/
Linfopoyesis
/
Proteínas Wnt
/
Vía de Señalización Wnt
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Hematol
Asunto de la revista:
HEMATOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos