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Autophagy markers expression pattern in developing liver of the yotari (dab1-/-) mice and humans
Edita Dražić Maras1, Nela Kelam2, Anita Racetin2
1Infectious Diseases Department, University Hospital of Split, Split 21000, Croatia.
Abstract:
Autophagy plays an important role in the physiology and pathology of the liver. Several negative autophagy regulators have been discovered, including epidermal growth factor receptor (EGFR), mediated by activation of the PI3K/Akt/mTOR signaling pathway. Disabled-1 (Dab1) is one of the mediating adaptor factors of PI3K/Akt/mTOR signaling pathways. We investigated the potential impact of Dab1 on autophagy-related markers (LC3B, LAMP2A, HSC70, and GRP78) in the developing liver by using a model of yotari mice and compared it with autophagy marker expression in human liver development. Mouse embryos were obtained at gestation days 13.5 and 15.5 (E13.5 and E15.5), and a total of 5 normal human conceptuses were obtained between gestation days 5 and 10. Histological sections were analyzed by immunohistochemistry. The highest expression of the early endosome-forming factor LC3B and the microautophagy factor LAMP2a was observed at the transition from embryonic to early fetal phase, whereas the expression of the chaperones HSC 70 and GRP78 was highest at embryonic phase. The expression patterns of three of these factors in mouse liver were different from those in human liver: the expression of LC3B was high at E13.5, that of HSC 70 at 15.5, whereas the expression of GRP78 did not change significantly. On the other hand, the expression pattern of LAMP2a was similar to that in human development and was higher at E15.5 than at E13.5. Moreover, knockout of Dab1 resulted in significantly lower expression of LC3B and LAMP2a in mouse embryo livers (at E13.5), indicating a possible role of Dab1 in regulating autophagy during embryonic development in the liver.
Insights
Disabled-1 (Dab1) influences liver autophagy during embryonic development. Dab1 knockout reduced key autophagy markers, LC3B and LAMP2a, in developing mouse livers, suggesting its regulatory role.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Autophagy is crucial for liver physiology and pathology.
- Epidermal growth factor receptor (EGFR) negatively regulates autophagy via the PI3K/Akt/mTOR pathway.
- Disabled-1 (Dab1) is an adaptor protein within the PI3K/Akt/mTOR signaling pathway.
Purpose of the Study:
- To investigate the impact of Dab1 on autophagy markers in developing liver.
- To compare autophagy marker expression in mouse and human liver development.
Main Methods:
- Utilized yotari mice model for embryonic liver studies.
- Analyzed autophagy markers (LC3B, LAMP2A, HSC70, GRP78) via immunohistochemistry.
- Examined mouse embryos at E13.5 and E15.5 and human conceptuses (gestation days 5-10).
Main Results:
- LC3B and LAMP2a expression peaked during the embryonic to early fetal transition.
- HSC70 and GRP78 expression were highest during the embryonic phase.
- Dab1 knockout significantly decreased LC3B and LAMP2a expression in embryonic mouse livers.
Conclusions:
- Dab1 plays a potential role in regulating autophagy during embryonic liver development.
- Autophagy marker expression patterns in mouse liver development differ from human development.
- LAMP2a expression patterns showed similarity between mouse and human liver development.
