生物
衰老
细胞生物学
脂滴
GDF15型
调解人
线粒体
下调和上调
细胞
脂毒性
内分泌学
内科学
基因
遗传学
医学
糖尿病
胰岛素抵抗
作者
Antonio Chiariello,Luca Rossetti,Luca Rossetti,Sabrina Valente,Gianandrea Pasquinelli,Gianandrea Pasquinelli,Manuela Sollazzo,Luisa Iommarini,Anna Maria Porcelli,Monica Tognocchi,Giuseppe Conte,Aurelia Santoro,Katarzyna Malgorzata Kwiatkowska,Paolo Garagnani,Paolo Garagnani,Stefano Salvioli,Stefano Salvioli,Maria Conte
摘要
Abstract Perilipin 2 (PLIN2) is a lipid droplet (LD)‐coating protein playing important roles in lipid homeostasis and suppression of lipotoxicity in different tissues and cell types. Recently, a role for PLIN2 in supporting mitochondrial function has emerged. PLIN2 dysregulation is involved in many metabolic disorders and age‐related diseases. However, the exact consequences of PLIN2 dysregulation are not yet completely understood. In this study, we knocked down (KD) PLIN2 in primary human dermal fibroblasts (hDFs) from young (mean age 29 years) and old (mean age 71 years) healthy donors. We have found that PLIN2 KD caused a decline of mitochondrial function only in hDFs from young donors, while mitochondria of hDFs from old donors (that are already partially impaired) did not significantly worsen upon PLIN2 KD. This mitochondrial impairment is associated with the increased expression of the stress‐related mitokine growth differentiation factor 15 (GDF15) and the induction of cell senescence. Interestingly, the simultaneous KD of PLIN2 and GDF15 abrogated the induction of cell senescence, suggesting that the increase in GDF15 is the mediator of this phenomenon. Moreover, GDF15 KD caused a profound alteration of gene expression, as observed by RNA‐Seq analysis. After a more stringent analysis, this alteration remained statistically significant only in hDFs from young subjects, further supporting the idea that cells from old and young donors react differently when undergoing manipulation of either PLIN2 or GDF15 genes, with the latter being likely a downstream mediator of the former.
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