Overexpression of PRDM16 attenuates acute kidney injury progression: genetic and pharmacological approaches

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 21, 2024

Acute kidney injury (AKI) presents as a condition marked by sudden and rapid decrease in function over short timeframe, resulting from diverse causes. As transcription factor, PR domain-containing 16 (PRDM16), has recently been implicated brown fat biogenesis heart diseases. Our recent works indicated that PRDM16 could suppress the occurrence of renal interstitial fibrosis diabetic disorder. Nonetheless, effect regulatory mechanism AKI remain elusive. study demonstrated inhibited apoptosis induced ischemic/reperfusion (I/R) BUMPT (Boston University mouse proximal tubular) cells HK-2(Human Kidney-2) cells. Mechanistically, not only bound to promoter region S100 Calcium Binding Protein A6 (S100A6)and upregulated its expression but also interacted with amino acids 945-949, 957-960, 981-984 p38MAPK JNK axes via inhibition PKC-η activity mitochondrial reactive oxygen species (ROS) production. Furthermore, cisplatin- I/R-stimulated progression were ameliorated proximal-tubule-specific knockin mice, whereas exacerbated knockout mice). Moreover, we observed formononetin I/R- cisplatin-triggered mice. Taken together, these findings reveal novel self-protective AKI, whereby regulates S100A6/PKC-η/ROS/p38MAPK pathways inhibit progression.

Language: Английский

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Exercise-regulated lipolysis: Its role and mechanism in health and diseases

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 135(3)

Published: Dec. 3, 2024

Disruptions of blood pressure (BP) circadian variation are closely associated with an increased risk cardiovascular disease (CVD). Thus, gaining insights into the molecular mechanisms BP is essential for comprehending regulation. Human genetic analyses suggest that PR domain-containing protein 16 (PRDM16), a transcription factor highly expressed in vascular smooth muscle cells (VSMC), significantly BP-related traits. However, roles PRDM16 regulation largely unknown. Here, we demonstrate VSMC-specific Prdm16 knockout (Prdm16SMKO) mice was lower than control during active period, resulting aberrant variation. Mesenteric artery rings from Prdm16SMKO showed reduced response to phenylephrine. Mechanistically, identified adrenergic receptor alpha 1d (Adra1d) as transcriptional target PRDM16. Notably, exhibits remarkable expression pattern and regulates clock genes, particularly Npas2, which crucial Consequently, deficiency VSMC causes disrupted through signaling gene Our findings offer substantial intricate pathways govern fluctuations BP.

Language: Английский

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Roles of distinct nuclear receptors in diabetic cardiomyopathy

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 24, 2024

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

Language: Английский

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Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 21, 2024

Language: Английский

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Attenuated NIX in impaired mitophagy contributes to exacerbating cellular senescence in experimental periodontitis under hyperglycemic conditions

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Premature accumulation of senescent cells results in tissue destruction, and it is one the potential primary mechanisms underlying accelerated progression diabetes periodontitis. However, whether this characterized phenomenon could account for periodontal pathogenesis under hyperglycemic conditions remains unclear. In study, we assessed phenotypic changes experimental periodontitis conditions. Next, investigated mitochondrial function mitophagy pathways cellular senescence vitro vivo. Our findings showed that significant occurred gingival tissues diabetic mice with increased expression senescence-related protein p21

Language: Английский

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Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with poor prognosis and the leading cause death in diabetic patients. Sleep deficiency not only recognized as an important risk factor for development type 2 DM, but also associated increased morbidity mortality disease. The underlying role mechanisms sleep restriction (SR) DCM are far from clear. KK/Upj-Ay mouse model T2 DM was used study subject, small animal ultrasound imaging system to detect function heart; immunopathological staining clarify histo-structural pathological alterations TUNEL staining, qPCR, transmission electron microscopy (TEM), ELISA kits were apoptosis, oxidative stress, inflammation, mitochondrial damage, related molecular alterations. SR led significant increase mortality, cardiac hypertrophy, necrosis, glycogen deposition fibrosis further deteriorated KK mice.SR cardiomyocyte mice through Bax/Bcl2 pathway. In addition this, exacerbated inflammatory response, aggravated damage promoted stress PRDM16-PGC-1α Overall, exacerbates structural dysfunction apoptosis mice, increasing death. Clinicians patients prompted pay attention habits avoid accelerating transition heart failure inducing due habits.

Language: Английский

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Intestinal Nogo-B reduces GLP1 levels by binding to proglucagon on the endoplasmic reticulum to inhibit PCSK1 cleavage

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 9, 2024

Glucagon-like peptide 1 (GLP1), which is mainly processed and cleaved from proglucagon in enteroendocrine cells (EECs) of the intestinal tract, acts on GLP1 receptor pancreatic to stimulate insulin secretion inhibit glucagon secretion. However, processing not fully understood. Here, we show that reticulon 4B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, interacts with major fragment retain ER, thereby inhibiting PCSK1-mediated cleavage Golgi. Intestinal Nogo-B knockout male type 2 diabetes mellitus (T2DM) mice increases levels decreases levels, alleviating injury resistance. Finally, identify aberrantly elevated expression inhibited EECs diabetic patients. Our study reveals subcellular regulatory processes involving during production suggests as a potential therapeutic target for T2DM. (GLP1) authors it GLP1.

Language: Английский

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CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing

Life Sciences, Journal Year: 2024, Volume and Issue: 358, P. 123176 - 123176

Published: Oct. 24, 2024

Language: Английский

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Recent Advances Associated with Cardiometabolic Remodeling in Diabetes-induced Heart Failure

AJP Heart and Circulatory Physiology, Journal Year: 2024, Volume and Issue: 327(6), P. H1327 - H1342

Published: Oct. 25, 2024

Diabetes mellitus (DM) is characterized by chronic hyperglycemia, and despite intensive glycemic control, the risk of heart failure in patients with diabetes remains high. Diabetes-induced (DHF) presents a unique metabolic challenge, driven significant alterations cardiac substrate metabolism, including increased reliance on fatty acid oxidation, reduced glucose utilization, impaired mitochondrial function. These lead to oxidative stress, lipotoxicity, energy deficits, contributing progression failure. Emerging research has identified novel mechanisms involved remodeling diabetic hearts, such as autophagy dysregulation, epigenetic modifications, polyamine regulation, branched-chain amino (BCAA) metabolism. processes exacerbate dysfunction inflexibility, further impairing Therapeutic interventions targeting these pathways—such enhancing modulating optimizing ketone body utilization—show promise restoring homeostasis improving outcomes. This review explores key molecular driving highlights advanced methodologies, latest therapeutic strategies for mitigating DHF. Understanding emerging pathways offers new opportunities develop targeted therapies that address root causes diabetes.

Language: Английский

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