Next Article in Journal
Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature
Next Article in Special Issue
Retinoic Acid and Germ Cell Development in the Ovary and Testis
Previous Article in Journal
Exploring Biological Activity of 4-Oxo-4H-furo[2,3-h]chromene Derivatives as Potential Multi-Target-Directed Ligands Inhibiting Cholinesterases, β-Secretase, Cyclooxygenase-2, and Lipoxygenase-5/15
Previous Article in Special Issue
Two Opposing Faces of Retinoic Acid: Induction of Stemness or Induction of Differentiation Depending on Cell-Type
Open AccessArticle

Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity

1
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary
2
Department of Dental Biochemistry, Faculty of Dentistry, University of Debrecen, Debrecen H-4012, Hungary
3
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary
4
Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary
5
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary
6
Paprika Bioanalytics BT, Debrecen H-4002, Hungary
7
Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada
8
Gavin Herbert Eye Institute and the Department of Ophthalmology, University of California, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 737; https://doi.org/10.3390/biom9110737
Received: 14 October 2019 / Revised: 7 November 2019 / Accepted: 9 November 2019 / Published: 13 November 2019
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvβ35 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage. View Full-Text
Keywords: retinol saturase; efferocytosis; MFG-E8; macrophage; autoimmunity; neuropeptide Y retinol saturase; efferocytosis; MFG-E8; macrophage; autoimmunity; neuropeptide Y
Show Figures

Figure 1

MDPI and ACS Style

Sarang, Z.; Sághy, T.; Budai, Z.; Ujlaky-Nagy, L.; Bedekovics, J.; Beke, L.; Méhes, G.; Nagy, G.; Rühl, R.; Moise, A.R.; Palczewski, K.; Szondy, Z. Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity. Biomolecules 2019, 9, 737.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop