All‐trans retinoic acid improves pancreatic cell proliferation on induced type 1 diabetic rats

Ramírez-Moreno, Agustina; Escorza, Martha Angélica Quintanar; García-Garza, Rubén; Keita, Hady; Valenzuela, Adrian Meléndez; Marszalek, Jolanta E.; Sharara‐Núñez, Ibrahim; Delgadillo‐Guzmán, Dealmy

doi:10.1111/fcp.12523

Cited by 7 publications

(9 citation statements)

References 31 publications

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“…ATRA may help to alleviate transfusion-related ALI ( 41 ). According to previous studies ( 32 , 42 – 44 ), olive oil is usually selected as the control of ATRA treatment. Accordingly, the present study used olive oil as the control of ATRA treatment.…”

Section: Discussionmentioning

confidence: 99%

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All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

Lei

et al. 2021

Mol Med Rep

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Acute lung injury (ALI) is a common clinical emergency and all-trans retinoic acid (ATRA) can alleviate organ injury. Therefore, the present study investigated the role of ATRA in ALI. Lipopolysaccharide (LPS)-induced ALI rats were treated with ATRA and the arterial partial pressure of oxygen (PaO 2 ), lung wet/dry weight (W/D) ratio and protein content in the bronchial alveolar lavage fluid (BALF) were measured to evaluate the effect of ATRA on ALI rats. Alveolar macrophages were isolated from the BALF. The phagocytic function of macrophages was detected using the chicken erythrocyte phagocytosis method and flow cytometry. The viability of macrophages was measured using a Cell Counting Kit-8 assay, and apoptosis was analyzed using a TUNEL assay and flow cytometry. The expression levels of Toll-like receptor 4 (TLR4) and cluster of differentiation (CD)14 on the macrophage membrane were detected by immunofluorescence staining. The protein levels of TLR4, CD14, phosphorylated (p)-65, p65, p-IκBα and IκBα were analyzed using western blotting. The concentrations of IL-6, IL-1β and macrophage inflammatory protein-2 in the plasma of rats were detected by ELISA. Macrophages were treated with IAXO-102 (TLR4 inhibitor) to verify the involvement of CD14/TLR4 in the effect of ATRA on ALI. ATRA provided protection against LPS-induced ALI, as evidenced by the increased PaO 2 and reduced lung W/D ratio and protein content in the BALF. ATRA enhanced macrophage phagocytosis and viability and reduced apoptosis and inflammation in ALI rats. Mechanically, ATRA inhibited CD14 and TLR4 expression and NF-κB pathway activation. ATRA enhanced macrophage phagocytosis and reduced inflammation by inhibiting the CD14/TLR4-NF-κB pathway in LPS-induced ALI. In summary, ATRA inactivated the NF-κB pathway by inhibiting the expression of CD14/TLR4 receptor in the alveolar macrophages of rats, thus enhancing the phagocytic function of macrophages in ALI rats, improving the activity of macrophages, inhibiting apoptosis, reducing the levels of inflammatory factors, and consequently playing a protective role in ALI model rats. This study may offer novel insights for the clinical management of ALI.

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Section: Discussionmentioning

confidence: 99%

“…A previous study showed that CD14 and TLR4 expression is increased in LPS-induced ALI ( 53 ). RA receptor agonists help to inhibit CD14 and TLR4 signaling and then suppress the NF-κB pathway ( 44 ). It has been demonstrated that TLR4 mediates the NF-κB pathway in macrophages and they serve a crucial role in ALI ( 27 , 28 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

Lei

et al. 2021

Mol Med Rep

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“…RA has been shown to have renoprotective effects in experimental models of diabetic kidney disease through an anti-inflammatory mechanism (47). Besides, RA may have beneficial effects on insulin sensitivity, the lipid profile, circulating adipocytokines (48), and pancreatic cell proliferation (49).…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

Disparate roles of retinoid acid signaling molecules in kidney disease

Chen

Liu

et al. 2021

American Journal of Physiology-Renal Physiology

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RA (Retinoid acid) is synthesized mainly in the liver and has multiple functions in development, cell differentiation and proliferation, and regulation of inflammation. RA has been used to treat multiple diseases such as cancer and skin disorders. The kidney is a major organ for RA metabolism, which is altered in the diseased condition. RA is known to have renal protective effects in multiple animal models of kidney disease. RA has been shown to ameliorate podocyte injury through induction of expression of differentiation markers and regeneration of podocytes from its progenitor cells in animal models of kidney disease. The effects of RA in podocytes are mediated mainly by activation of cAMP/PKA pathway via retinoic acid receptor-α (RARα) and activation of its downstream transcription factor KLF15. Screening of RA signaling molecules in human kidney disease reveals RARRES1 as a risk gene for glomerular disease progression. RARRES1, a podocyte-specific growth arrest gene, is regulated by both high doses of RA and TNFα. Mechanistically, RARRES1 is cleaved by MMPs to generate soluble RARRES1 which then induces podocyte apoptosis through interaction with intracellular RIOK1. Therefore, a high dose of RA may induce podocyte toxicity through the upregulation of RARRES1. Based on the current findings, to avoid potential side effects we propose three strategies to develop future therapies of RA for glomerular disease: 1) develop RARα- and KLF15-specific agonists; 2) use the combination of a low dose of RARα agonist with PDE4 inhibitors; and 3) use the combination of RARα agonist with RARRES1 inhibitors.

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“…RA treatment (0.5 mg/mouse intraperitoneally every other day) for 6 weeks is able to delay the onset of diabetes in NOD/Scid mice [85]. In alloxan-induced type 1 diabetic rats, RA treatment (0.20 mg/kg) for 17 days is able to reduce the blood glucose [86]. Both mouse and rat studies have attributed the benefits of RA treatment to the improvement of pancreatic β cell functions [85,86].…”

Section: The Effects Of Ra On Metabolismmentioning

confidence: 99%

“…In alloxan-induced type 1 diabetic rats, RA treatment (0.20 mg/kg) for 17 days is able to reduce the blood glucose [86]. Both mouse and rat studies have attributed the benefits of RA treatment to the improvement of pancreatic β cell functions [85,86]. More studies are needed to understand the roles of VA in the control of pancreatic functions, as discussed in [84].…”

Section: The Effects Of Ra On Metabolismmentioning

confidence: 99%

The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

Chen

2021

Cells

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The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA’s physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.

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All‐trans retinoic acid improves pancreatic cell proliferation on induced type 1 diabetic rats

Cited by 7 publications

References 31 publications

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

Disparate roles of retinoid acid signaling molecules in kidney disease

The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

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