Abstract
Collagen XIX is a nonfibrillar collagen that localizes in restricted tissues at very low amounts. A previous study on Col19a1 null mice revealed that collagen XIX is involved in esophageal muscle physiology and morphogenesis. Here, we use histological analysis to show that mice with a Col19a1 mutant lacking the NC3 domain and seven collagen triplets display abnormal transition of smooth to striated muscle in the abdominal segment of esophagus, and a widened esophagus with age. With two newly prepared antibodies, we analyzed the expression of collagen XIX in the mouse esophagus and show that collagen XIX colocalizes with α-smooth muscle actin. By immunoelectron microscopy, we confirmed the localization of collagen XIX in esophageal smooth muscle cells. Col19a1 mutant mice contained reduced levels of mutated Col19a1 mRNA. Interestingly, hepatocyte growth factor, which has an important role in esophageal striated muscle development, was reduced in the esophagus of the Col19a1 mutant mice. These findings suggest that collagen XIX may be critical for the function of esophageal smooth muscle cells as a scaffold for anteroposterior migration of esophagus-striated muscle cells.
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Data availability
The data that support the findings of this study and the antibodies which generated for this study are available from the corresponding author upon reasonable request.
Abbreviations
- LES:
-
Lower esophageal sphincter
- ESM:
-
Esophagus striated muscle
- HGF:
-
Hepatocyte growth factor
- NC domain:
-
Noncollagenous domain
- ∆19 mice:
-
Col19a1 mutant mice that lack the NC3 domain and seven collagenous triplets
- HRP:
-
Horseradish peroxidase
- NGS:
-
Normal goat serum
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Acknowledgements
The authors thank Ai Uezono, a former master student in the department of Matrix Medicine for her contribution to the beginning of this study, Dr. Noritaka Matsuo for his support on this project and Dr. Boudko (Vanderbilt University Medical Center) for providing the expression plasmid and the cDNA of COL19A1. We are grateful to Professor Klaus von der Mark (University of Erlangen-Nürnberg, Germany) for his valuable comments and editing the manuscript.
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HS, KJ, HK, AY, SA, and TS performed experiments. SY analyzed using an electron microscopy. HK, HY, and TS designed the experiments, supervised the project, and wrote the manuscripts.
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All animal experiments were conducted in accordance with the experimental protocols approved by the Animal Care and Use Committee of Oita University.
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Sato, H., Jin, K., Yano, S. et al. Abnormalities in esophageal smooth muscle induced by mutations in collagen XIX. Histochem Cell Biol 157, 205–216 (2022). https://doi.org/10.1007/s00418-021-02059-9
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DOI: https://doi.org/10.1007/s00418-021-02059-9