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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

pididymal embryonic development harbors TLR4/NFKB signaling pathway as a morphogenetic playe

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Autor(es):
Ferreira, Lucas G. A. [1] ; Nishino, Fernanda A. [1] ; Fernandes, Samuel G. [1] ; Ribeiro, Camilla M. [1, 2] ; Hinton, Barry T. [3] ; Avellar, Maria Christina W. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, BR-04044020 Sao Paulo, SP - Brazil
[2] Ctr Univ Planalto Araxa UNIARAXA, BR-38180084 Araxa, MG - Brazil
[3] Univ Virginia Hlth Syst, Dept Cell Biol, Charlottesville, VA 22903 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF REPRODUCTIVE IMMUNOLOGY; v. 149, FEB 2022.
Citações Web of Science: 0
Resumo

The Wolffian duct (WD) is an embryonic tissue that undergoes androgen-induced morphological changes to become the epididymis. Toll-like receptor 4 (TLR4)- and nuclear factor kB (NFKB)-induced effectors are expressed in the adult epididymis and represent important players in epididymal innate immune responses. TLR4/NFKB signaling pathway is evolutionarily conserved and plays a critical morphogenetic role in several species; however, its function during WD morphogenesis is unknown. We hypothesized that TLR4/NFKB pathway plays a role during WD development. Here we examined TLR4 expression and regulation of TLR4-target genes during rat WD morphogenesis between embryonic days (e) 17.5-20.5. The functionality of TLR4/NFKB signaling was examined using WD organotypic cultures treated with lipopolysaccharide (LPS) from E. coli (TLR4 agonist) and PDTC (NFKB inhibitor). TLR4 was detected at mRNA level in e17.5 (uncoiled duct) and e20.5 (coiled duct) WDs, and spatio-temporal changes in TLR4 immunoreactivity were observed between these two time points. Expression level analysis of a subset of TLR4-regulated genes showed that TLR4/NFKB pathway was activated after exposure of cultured WD to LPS (4 h), an event that was abrogated by PDTC. Long-term exposure of cultured WDs to LPS (96 h) resulted in dysregulations of morphogenetic events and LAMA1 immunodistribution changes, suggesting the extracellular matrix at the intersection between WD morphogenesis and balance of innate immune components. Our results unveil the epididymal morphogenesis as an event equipped with TLR4/NFKB signaling components that may serve developmental functions, and eventually transition to host defense function when the fetus is exposed to an infectious or noninfectious threat. (AU)

Processo FAPESP: 16/22118-1 - Regulação androgênica, atividade biológica e sinalização celular de beta-defensinas na morfogênese do epidídimo
Beneficiário:Lucas Garcia Alves Ferreira
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 19/02633-7 - Investigação dos mecanismos de ação e função de componentes da imunidade inata na morfogênese do epidídimo
Beneficiário:Fernanda Akane Nishino
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica