BMP7 is Downregulated in Lumbosacral Spinal Cord of Rat Embryos With Anorectal Malformation

Copyright © 2019. Published by Elsevier Inc..

BACKGROUND: Bone morphogenetic proteins (BMPs) comprise a highly conserved signaling protein family, which are involved in spinal cord formation, development and differentiation. Malformations of the lumbosacral spinal cord are associated with postoperation complications of anorectal malformation (ARM). However, the mechanism underlying the development of these malformations remains elusive.

MATERIALS AND METHODS: Embryonic rat ARM model induced by ethylenethiourea (ETU) was introduced to investigate BMP7 expression in lumbosacral spinal cord. BMP7 expression was analyzed by immunohistochemical staining, qRT-PCR, and Western blot analysis on embryonic (E) days 16, 17, 19, and 21. The expression of the neuronal marker neurofilament (NF) and pSmad1/5 was determined by immunofluorescence double staining and Western blot analysis during peak BMP7 expression.

RESULTS: BMP7 mRNA (E16, 1.041 ± 0.169 versus 0.758 ± 0.0423, P < 0.05; E17, 1.889 ± 0.444 versus 1.601 ± 0.263, P < 0.05; E19, 2.898 ± 0.434 versus 1.981 ± 0.068, P < 0.01; and E21, 2.652 ± 0.637 versus 1.957 ± 0.09, P < 0.05;) and protein (E16, 1.068 ± 0.065 versus 0.828 ± 0.066, P < 0.01; E17, 1.728 ± 0.153 versus1.4 ± 0.148, P < 0.05; E19, 2.313 ± 0.141 versus 1.696 ± 0.21, P < 0.01; and E21, 2.021 ± 0.13 versus 1.43 ± 0.128, P < 0.01) were downregulated, and their expressions were specifically low in interneurons (IN) located in the dorsal horn of the lumbosacral spinal cord in embryos with ARM. On E19, Western blot analysis revealed reduced P-Smad1/5(1.13 ± 0.08 versus 0.525 ± 0.06, P < 0.01).

CONCLUSIONS: An implication of this study is the possibility that BMP7 downregulation contributes to maldevelopment of the lumbosacral spinal cord during embryogenesis in fetal rats with ARM, indicating that BMP7 may play an important role in ARM pathogenesis and the complications thereof.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:251

Enthalten in:

The Journal of surgical research - 251(2020) vom: 15. Juli, Seite 202-210

Sprache:

Englisch

Beteiligte Personen:

Yang, Zhonghua [VerfasserIn]
Li, Xiang [VerfasserIn]
Jia, Huimin [VerfasserIn]
Bai, Yuzuo [VerfasserIn]
Wang, Weilin [VerfasserIn]

Links:

Volltext

Themen:

Anorectal malformation
BMP7
Bmp7 protein, rat
Bone Morphogenetic Protein 7
Development
Journal Article
Lumbosacral spinal cord
Neuron
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 14.09.2020

Date Revised 14.09.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jss.2019.11.020

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307577643