Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Yoshida, Yuya; Matsumoto, Naoya; Nakao, Takahiro; Hamamura, Keisuke; Kondo, Hideaki; Ide, Tomomi; Tsutsui, Hiroyuki; Tsuruta, Akito; Kurogi, Masayuki; Nakaya, Michio; Kurose, Hitoshi; Koyanagi, Satoru; Ohdo, Shigehiro

doi:10.1038/s41467-021-23050-x

Cited by 51 publications

(25 citation statements)

References 84 publications

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“…In addition, local inflammation and concomitant hypoxia are themselves additional factors causing local acidification [20]. Activation of proton-activated GPCRs has been implicated in the regulation of inflammatory processes that span from the infiltration of immune cells to their differentiation, proliferation, and activity [7,27,120,136,153]. The abundant expression of GPR4 in endothelial cells allows to mediate at least in part the pH-dependent activation of endothelial cells and subsequent immune cell invasion [58,92].…”

Section: A Brief Overview On the Role Of Proton-activated Gpcrs In Or...mentioning

confidence: 99%

Physiological relevance of proton-activated GPCRs

Silva

Wagner

2022

Pflugers Arch - Eur J Physiol

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The detection of H+ concentration variations in the extracellular milieu is accomplished by a series of specialized and non-specialized pH-sensing mechanisms. The proton-activated G protein–coupled receptors (GPCRs) GPR4 (Gpr4), TDAG8 (Gpr65), and OGR1 (Gpr68) form a subfamily of proteins capable of triggering intracellular signaling in response to alterations in extracellular pH around physiological values, i.e., in the range between pH 7.5 and 6.5. Expression of these receptors is widespread for GPR4 and OGR1 with particularly high levels in endothelial cells and vascular smooth muscle cells, respectively, while expression of TDAG8 appears to be more restricted to the immune compartment. These receptors have been linked to several well-studied pH-dependent physiological activities including central control of respiration, renal adaption to changes in acid–base status, secretion of insulin and peripheral responsiveness to insulin, mechanosensation, and cellular chemotaxis. Their role in pathological processes such as the genesis and progression of several inflammatory diseases (asthma, inflammatory bowel disease), and tumor cell metabolism and invasiveness, is increasingly receiving more attention and makes these receptors novel and interesting targets for therapy. In this review, we cover the role of these receptors in physiological processes and will briefly discuss some implications for disease processes.

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Section: A Brief Overview On the Role Of Proton-activated Gpcrs In Or...mentioning

confidence: 99%

Physiological relevance of proton-activated GPCRs

Silva

Wagner

2022

Pflugers Arch - Eur J Physiol

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“…Activation of NF-κB produces a series of in ammatory cytokines, such as IL-6, IL-1β, IL-12, TNFa. In this in ammatory cytokines, IL-6 plays a central role in body defense by stimulating various cell populations and is an essential part of the in ammatory mediator network [39,40] . In recent years, HIF-1/ NF-κB is being increasingly recognized as a critical factor in the in ammatory response.…”

Section: Discussionmentioning

confidence: 99%

Latifolin enhances both survival and cardiomyocyte differentiation of bone marrow mesenchymal stem cells on rat myocardial infarction model

Zhang

Lai

Chen

et al. 2022

Preprint

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Background: Myocardial infarction caused abundant loss of cardiomyocytes and myocardium limited self-repair ability. Mesenchymal stem cells (MSCs) were a promising option for cardiomyocyte regeneration therapies. However, low cardiomyocyte differentiation efficiency and poor cell survival limit application in myocardial infarction. Here, our study aimed to promote the survival and cardiomyocyte differentiation of BM-MSCs by latifolin from Dalbergiae Odoriferae. Methods: In vitro, cell survival was measured by MTT and apoptosis assays. BM-MSCs morphological differentiation was observed under microscope and TEM. Cardiac-specific genes and proteins were measured by RT-PCR and immunofluorescence staining. In vivo, cardiac function was assessed by LDH and CK-MB and echocardiography. The gross morphology and TTC were used to assess the LV infarct size. Masson’s trichrome was used to detect the extent of fibrosis. Histopathological changes were observed by HE staining. Immunofluorescence was used to detect the survival and cardiomyocyte differentiation of BM-MSCs. Immunohistochemistry was used to detect macrophage CD68 and neutrophils MPO expression. The protein expression of IL-6, p-NF-κB, β-catenin and HIF-1αwere detected by Western Blot. Results: In vitro, latifolin increased BM-MSCs viability and decreased apoptosis. Both atrial particles and myofilaments were precisely observed in the cytoplasm under TEM. Latifolin increased the cardiac-specific mRNA and proteins. In vivo, latifolin promoted BM-MSCs to reduce myocardial enzyme and improve cardiac function. Moreover, latifolin promoted BM-MSCs to reduces myocardial infarction size, myocardial fibrosis size, histopathological changes and macrophage infiltration in myocardial tissue. At the same time, latifolin promoted survival and cardiomyocyte differentiation of BM-MSCs. Latifolin up-regulated the protein expression of β-catenin and down-regulated the protein expression of IL-6, p-NF-κB, HIF-1α. Conclusion: Latifolin enhanced the effect of BM-MSCs to cure MI by promoting survival and cardiomyocyte differentiation after transplant in myocardial tissue though HIF-1α/NF-κB/IL-6 pathway and HIF-1α/β-catenin pathway. Such pro-differentiation and pro-survival might be a potential strategy to increase their regenerative efficacy.

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“…Not unexpectedly, chronic kidney disease (CKD) can also increase RBP4 in the circulation [ 172 ]. Experimentally, a 5/6 nephrectomy in mice increased concentrations of retinol and RBP4 in blood, which promoted the expression of G protein-coupled receptor-68 in circulating monocytes [ 173 ]. Cardiac infiltration of these monocytes under CKD conditions may exacerbate inflammation and fibrosis of the heart.…”

Section: Rbp4 In Health and Diseasementioning

confidence: 99%

Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease

2022

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Retinol binding protein 4 (RBP4) is the specific transport protein of the lipophilic vitamin A, retinol, in blood. Circulating RBP4 originates from the liver. It is secreted by hepatocytes after it has been loaded with retinol and binding to transthyretin (TTR). TTR association prevents renal filtration due to the formation of a higher molecular weight complex. In the circulation, RBP4 binds to specific membrane receptors, thereby delivering retinol to target cells, rendering liver-secreted RBP4 the major mechanism to distribute hepatic vitamin A stores to extrahepatic tissues. In particular, binding of RBP4 to ‘stimulated by retinoic acid 6’ (STRA6) is required to balance tissue retinoid responses in a highly homeostatic manner. Consequently, defects/mutations in RBP4 can cause a variety of conditions and diseases due to dysregulated retinoid homeostasis and cover embryonic development, vision, metabolism, and cardiovascular diseases. Aside from the effects related to retinol transport, non-canonical functions of RBP4 have also been reported. In this review, we summarize the current knowledge on the regulation and function of RBP4 in health and disease derived from murine models and human mutations.

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Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Cited by 51 publications

References 84 publications

Physiological relevance of proton-activated GPCRs

Physiological relevance of proton-activated GPCRs

Latifolin enhances both survival and cardiomyocyte differentiation of bone marrow mesenchymal stem cells on rat myocardial infarction model

Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease

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