Retinoic Acid and Retinoid X Receptors

Schubert, Michael; Germain, Pierre

doi:10.3390/cells12060864

Cited by 3 publications

References 33 publications

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Retinoic acid receptor alpha inhibits ferroptosis by promoting thioredoxin and protein phosphatase 1F in lung adenocarcinoma

Bian,

Shan,

Liang

et al. 2024

Commun Biol

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Ferroptosis is a recently discovered form of cell death that plays an important role in tumor growth and holds promise as a target for antitumor therapy. However, evidence in the regulation of ferroptosis in lung adenocarcinoma (LUAD) remains elusive. Here, we show that retinoic acid receptor alpha (RARA) is upregulated with the treatment of ferroptosis inducers (FINs). Pharmacological activation of RARA increases the resistance of LUAD to ferroptosis according to cell viability and lipid peroxidation assays, while RARA inhibitor or knockdown (KD) does the opposite. Through transcriptome sequencing in RARA-KD cells and chromatin immunoprecipitation (CHIP)-Seq data, we identify thioredoxin (TXN) and protein phosphatase 1 F (PPM1F) as downstream targets of RARA, both of which inhibit ferroptosis. We confirm that RARA binds to the promotor region of TXN and PPM1F and promotes their transcription by CHIP-qPCR and dual-luciferase assays. Overexpression of TXN and PPM1F reverses the effects of RARA knockdown on ferroptosis in vitro and vivo. Clinically, RARA knockdown or inhibitor increases cells’ sensitivity to pemetrexed and cisplatin (CDDP). Immunohistochemistry (IHC) of LUAD from our cohort shows the same expression tendency of RARA and the downstream targets. Our study uncovers that RARA inhibits ferroptosis in LUAD by promoting TXN and PPM1F, and inhibiting RARA-TXN/PPM1F axis represents a promising strategy for improving the efficacy of FINs or chemotherapy in the treatment of LUAD patients.

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Retinoic acid receptor alpha inhibits ferroptosis by promoting thioredoxin and protein phosphatase 1F in lung adenocarcinoma

Bian,

Shan,

Liang

et al. 2024

Commun Biol

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Human macula formation involves two waves of retinoic acid signaling suppression viaCYP26A1regulating cell cycle exit and cone specification

Harding,

Wojtynska,

Smith

et al. 2024

Preprint

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The human macula is a specialized, M/L cone-rich region of the eye, critical for high acuity vision, but little is known about the pathways regulating its development. Transcriptional regulation by Retinoic Acid (RA) is essential for many aspects of human eye development. Here, we report a striking biphasic expression of the RA-catabolizing enzyme, CYP26A1, in early human macular development between post-conception weeks 6-17. Early inhibition of RA signaling in human retinal organoids (hROs) prompts early cell cycle exit, and an increase in cone photoreceptors, while late inhibition alters cone subtype specification. Conversely, FGF8, which is negatively regulated by RA and vital for High Acuity Area specification in chick, is not expressed in the nascent human macula and had no effect on hRO photoreceptor fate.

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Roles of distinct nuclear receptors in diabetic cardiomyopathy

Zheng,

Xu,

et al. 2024

Front. Pharmacol.

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Diabetes mellitus induces a pathophysiological disorder known as diabetic cardiomyopathy and may eventually cause heart failure. Diabetic cardiomyopathy is manifested with systolic and diastolic contractile dysfunction along with alterations in unique cardiomyocyte proteins and diminished cardiomyocyte contraction. Multiple mechanisms contribute to the pathology of diabetic cardiomyopathy, mainly including abnormal insulin metabolism, hyperglycemia, glycotoxicity, cardiac lipotoxicity, endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, calcium treatment damage, programmed myocardial cell death, improper Renin-Angiotensin-Aldosterone System activation, maladaptive immune modulation, coronary artery endothelial dysfunction, exocrine dysfunction, etc. There is an urgent need to investigate the exact pathogenesis of diabetic cardiomyopathy and improve the diagnosis and treatment of this disease. The nuclear receptor superfamily comprises a group of transcription factors, such as liver X receptor, retinoid X receptor, retinoic acid-related orphan receptor-α, retinoid receptor, vitamin D receptor, mineralocorticoid receptor, estrogen-related receptor, peroxisome proliferatoractivated receptor, nuclear receptor subfamily 4 group A 1(NR4A1), etc. Various studies have reported that nuclear receptors play a crucial role in cardiovascular diseases. A recently conducted work highlighted the function of the nuclear receptor superfamily in the realm of metabolic diseases and their associated complications. This review summarized the available information on several important nuclear receptors in the pathophysiology of diabetic cardiomyopathy and discussed future perspectives on the application of nuclear receptors as targets for diabetic cardiomyopathy treatment.

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Retinoic Acid and Retinoid X Receptors

Abstract: One of the most fundamental discoveries in human biology was that of the existence of essential micronutrients that the body cannot synthesize but nonetheless requires for proper functioning [...]

Cited by 3 publications

References 33 publications

Retinoic acid receptor alpha inhibits ferroptosis by promoting thioredoxin and protein phosphatase 1F in lung adenocarcinoma

Retinoic acid receptor alpha inhibits ferroptosis by promoting thioredoxin and protein phosphatase 1F in lung adenocarcinoma

Human macula formation involves two waves of retinoic acid signaling suppression viaCYP26A1regulating cell cycle exit and cone specification

Roles of distinct nuclear receptors in diabetic cardiomyopathy

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