Journal of Cellular Physiology最新文献

Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate and lactate, critically shaping immune responses and cell functions in various diseases. Periodontitis is a chronic inflammatory disease marked by progressive destruction of periodontal tissues. Recent evidence has revealed that glycolysis plays a critical and dual role in periodontitis. On one hand, metabolic reprogramming toward glycolysis amplifies inflammatory cascades in various periodontal cells, driving periodontitis progression through multiple mechanisms. On the other hand, the end-product of glycolysis, lactate, and its lactylation exert anti-inflammatory effects in periodontitis by modulating immune responses and regulating bone remodeling. Moreover, emerging therapeutic strategies targeting glycolytic flux aim to inhibit periodontal inflammation progression and promote periodontal tissue regeneration. In this review, we illustrate the dual mechanisms of glycolysis in periodontitis pathogenesis and highlight its potential as a therapeutic target for metabolic intervention.

Type 2 diabetes (T2D) and Alzheimer's Disease (AD) have seemingly different pathologies and symptoms. However, T2D is a risk factor for AD, and recent evidence suggests there are many mechanistic similarities between the etiologies of each disease including inflammation. Mast cells are tissue resident, sentinel immune cells that reside in the pancreas, adipose tissue, and brain, increase in T2D and AD, and have generally been shown to worsen T2D and AD. However, there are limited studies of local or temporal mast cell deletion, and different phenotypic and polarization states seemingly influence the role of mast cells in the progression of disease. As there are metabolic similarities between T2D and AD including insulin resistance and lipid influx into the brain, we discuss the impact of glucose, insulin, amylin, and different lipid species on the activation and polarization of mast cells, which generally reduce IgE-mediated degranulation and promote lipid droplet formation and arachidonic acid metabolism. Altogether, this review provides a framework for understanding a shared mechanism of immunometabolic regulation of T2D and AD and provides rationale for future work in this area.

Ovarian granulosa cells (GCs) are pivotal for follicular homeostasis, and their dysregulated apoptosis drives age-related ovarian aging. The Hippo signaling pathway, modulated by long noncoding RNAs (lncRNAs), is implicated in regulating GCs proliferation and ovarian aging. TEAD2 (Transcriptional Enhanced Associate Domain 2), a key downstream transcription factor of the Hippo signaling pathway, plays a critical role in regulating cell proliferation, apoptosis, and embryonic stem cell self-renewal. However, the precise molecular mechanisms by which lncRNAs influence the Hippo pathway in GCs are not fully understood. Through comprehensive RNA-seq analysis of ovarian tissues across three distinct age groups (3-, 11-, and 17-month-old mice), we identified lnc81 as a senescence-associated lncRNA that physically interacts with TEAD2. RNA immunoprecipitation (RIP) assays demonstrated direct binding between lnc81 and TEAD2, while subcellular fractionation coupled with qRT-PCR revealed predominant nuclear localization of lnc81 in granulosa cells (GCs). Importantly, lnc81 expression exhibited a progressive, age-dependent elevation during ovarian aging. Functional characterization showed that lnc81 knockdown in GCs significantly: (i) Inhibited cellular proliferation (as evidenced by decreased Pcna expression). (ii) Promoted apoptosis (indicated by increased BAX/BCL-2 ratio and elevated TUNEL-positive cells). Mechanistically, while lnc81 depletion upregulated CCN1/CCN2 protein levels, it did not affect TEAD2 expression, suggesting that lnc81 regulates TEAD2 transcriptional activity rather than modulating its protein stability. Our findings highlight lnc81 as a nuclear lncRNA that interacts with TEAD2 to amplify CCN1/CCN2 signaling, thereby promoting GC apoptosis and ovarian aging. This mechanistic insight positions lnc81 as a potential biomarker for age-related ovarian decline and a candidate target for therapeutic intervention.

Excessive inflammation is a capital cause of scar formation and inflammation microenvironment that result in challenge of axonal regeneration after spinal cord injury (SCI). Macrophages and astrocytes play important roles in the inflammatory response. Tip cells, a critical endothelial sub-population, play pivotal roles in post-injury vascular regeneration. Nevertheless, their characteristics in SCI remain poorly documented. This study based on single cell RNA sequencing (scRNA-seq) and in vitro experiment, investigates the effects of tip cells on astrocytes and macrophages. For astrocytes, tip cells can recruit astrocytes to migrant, contribute to the formation of fence-like structure of astrocytes, finally inhibit the diffusion of inflammation via the Angptl4-Sdc4 ligand-receptor pathway. For macrophages, similarly through the Angptl4-Sdc4 ligand-receptor pathway, tip cells can promote macrophages to polarize more toward the M2 phenotype and inhibit their polarization toward M1 phenotype, thus alleviate the inflammatory response. Tip cells after SCI exhibit conserved ribosomal protein expression, implicating ribosome-dependent signaling in their function. These finding highlight the critical role of tip cells in microenvironment after SCI, offering a potential treatment target for SCI.

Ghrelin is a peptide hormone primarily produced by ghrelin cells in the stomach, playing a vital role in the regulation of eating behavior. Adenyl cyclase 8 (ADCY8), a key downstream signaling factor of G protein-coupled receptors, is essential for maintaining energy homeostasis by modulating levels of cyclic adenosine monophosphate (cAMP). Nevertheless, how ADCY8 modulates ghrelin levels and affects food intake is not well understood. Our findings demonstrated that Adcy8^−/− mice exhibited elevated levels of ghrelin and increased food consumption under both normal and high-fat diet conditions. These changes were associated with a reduction in the activity of the cAMP-PKA-mTOR signaling pathway within the gastric mucosa. The administration of the ghrelin receptor antagonist d-Lys-3-GH-releasing peptide-6 significantly decreased calorie intake in both wild-type and Adcy8^−/− mice. Furthermore, forskolin was shown to inhibit ghrelin and calorie intake in normal mice, an effect that was absent in Adcy8^−/− mice. Treatment with forskolin or overexpression of Adcy8 in both primary ghrelin-producing cells and mHypoE-42 cells resulted in decreased ghrelin levels, accompanied by activation of the cAMP-PKA-mTOR signaling pathway. Conversely, the use of the inhibitor SQ22536 or knockdown of Adcy8 produced opposing effects. In conclusion, gastric ADCY8 regulates the expression and secretion of ghrelin via the cAMP-PKA-mTOR signaling pathway, thereby influencing food intake.