Retinoic Acid Synthesis and Degradation

Kedishvili, Natalia Y.

doi:10.1007/978-94-024-0945-1_5

Cited by 95 publications

(106 citation statements)

References 184 publications

(231 reference statements)

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“…Retinoic acid (RA) biosynthesis and signaling (Fig. ) is another crucial role of the ALDHs, with the conversion of retinal to RA performed by three isozymes in the ALDH1 family, specifically ALDH1A1 (RALDH1), ALDH1A2 (RALDH2) and ALDH1A3 (RALDH3) . Research also implicates increased ALDH activity within tumors in the pathogenesis of various carcinomas and resistance to cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

Aldehyde dehydrogenase in regulatory T‐cell development, immunity and cancer

et al. 2018

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The role of aldehyde dehydrogenase (ALDH) in carcinogenesis and resistance to cancer therapies is well known. Mounting evidence also suggests a potentially important role for ALDH in the induction and function of regulatory T (Treg) cells. Treg cells are important cells of the immune system involved in promoting immune tolerance and preventing aberrant immune responses to beneficial or non-harmful antigens. However, Treg cells also impair tumor immunity, leading to the progression of various carcinomas. ALDH expression and the subsequent production of retinoic acid by numerous cells, including dendritic cells, macrophages, eosinophils and epithelial cells, seems important in Treg induction and function in multiple organ systems. This is particularly evident in the gastrointestinal tract, pulmonary tract and skin, which are exposed to a myriad of environmental antigens and represent interfaces between the human body and the outside world. Expression of ALDH in Treg cells themselves may also be involved in the proliferation of these cells and resistance to certain cytotoxic therapies. Hence, inhibition of ALDH expression may be useful to treat cancer. Besides the direct effect of ALDH inhibition on carcinogenesis and resistance to cancer therapies, inhibition of ALDH could potentially augment the immune response to tumor antigens by inhibiting Treg induction, function and ability to promote immune tolerance to tumor cells in multiple cancer types.

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Section: Introductionmentioning

confidence: 99%

Aldehyde dehydrogenase in regulatory T‐cell development, immunity and cancer

et al. 2018

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“…Retinoic acid synthesis depends on the 2-step conversion of vitamin A into retinaldehyde and retinoic acid respectively. The final and irreversible step of this conversion involves members of the aldehyde dehydrogenase enzyme family; Aldh1a1, Aldh1a2, Aldh1a3 and expression of these enzymes identifies cells that produce retinoic acid (Kedishvili, 2016). It is known that stromal cells as well as dendritic cells in adult lymph nodes express Aldh1 enzymes (Hammerschmidt et al, 2008; Molenaar et al, 2011), but the expression during early post-natal lymph node development has not been studied before.…”

Section: Resultsmentioning

confidence: 99%

Development of follicular dendritic cells in lymph nodes depends on retinoic acid mediated signaling

Koning

Rajaraman

Reijmers

et al. 2020

Preprint

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Specialized stromal cells occupy and help define B- and T cell domains, which is crucial for proper functioning of our immune system. Signaling through lymphotoxin and TNF-receptors is crucial for development of different stromal subsets which are thought to arise from a common precursor. However, mechanisms that control the selective generation of the different stromal phenotypes are not known.Here we show that in mice, retinoic acid mediated signaling is important for the differentiation of precursors towards the Cxcl13pos follicular dendritic cell (FDC) lineage, while blocking lymphotoxin mediated Ccl19pos fibroblastic reticular cell (FRC) lineage differentiation. Consequently, we see at day of birth Cxcl13posCcl19neg/low and Cxcl13neg/lowCcl19pos cells within neonatal lymph nodes.Furthermore, ablation of retinoic acid receptor signaling in stromal precursors early after birth reduces Cxcl13 expression, while in addition, complete blockade of retinoic acid signaling prevents formation of FDC networks in lymph nodes.

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“…These effects are likely to be indirect because isoprenoids are a large class of molecules with diverse functions. Retinoids are an isoprenoids derivative 65 and retinoic acid is one potential regulator of blood cell differentiation because previous studies have established that retinoic acid signaling increases the number of HSCs 30,31,33 and mediates the formation of HSCs from the mesoderm 66 . However, these mechanisms are likely to be complex and stage specific because retinoic acid has been shown to decrease the expression of gata1 in zebrafish 67 .…”

Section: Discussionmentioning

confidence: 99%

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

Hernández

Castro

Reyes-Nava

et al. 2018

Preprint

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word count: 187 Number of figures and tables: 5 Number of references: 72 Key Points 1. The products of the cholesterol synthesis pathway regulate red blood cell development during primitive erythropoiesis. 2. Isoprenoids regulate erythropoiesis by modulating the expression of the GATA1 transcription factor. AbstractErythropoiesis is the process by which new red blood cells (RBCs) are formed and defects in this process can lead to anemia or thalassemia. The GATA1 transcription factor is an established mediator of RBC development. However, the upstream mechanisms that regulate the expression of GATA1 are not completely characterized. Cholesterol is one potential upstream mediator of GATA1 expression because previously published studies suggest that defects in cholesterol synthesis disrupt RBC differentiation. Here we characterize RBC development in a zebrafish harboring a single missense mutation in the hmgcs1 gene (Vu57 allele). hmgcs1 encodes the first enzyme in the cholesterol synthesis pathway and mutation of hmgcs1 inhibits cholesterol synthesis. We analyzed the number of RBCs in hmgcs1 mutants and their wildtype siblings. Mutation of hmgcs1 resulted in a decrease in the number of mature RBCs, which coincides with reduced gata1a expression. We combined these experiments with pharmacological inhibition and confirmed that cholesterol and isoprenoid synthesis are essential for RBC differentiation, but that gata1a expression is isoprenoid dependent. Collectively, our results reveal two novel upstream regulators of RBC development and suggest that appropriate cholesterol homeostasis is critical for primitive erythropoiesis.

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Retinoic Acid Synthesis and Degradation

Cited by 95 publications

References 184 publications

Aldehyde dehydrogenase in regulatory T‐cell development, immunity and cancer

Aldehyde dehydrogenase in regulatory T‐cell development, immunity and cancer

Development of follicular dendritic cells in lymph nodes depends on retinoic acid mediated signaling

Mutations in the zebrafishhmgcs1gene reveal a novel function for isoprenoids during red blood cell development

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