The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis
JOURNAL OF LEUKOCYTE BIOLOGY
Authors: Ohradanova-Repic, Anna; Machacek, Christian; Donner, Clemens; Muehlgrabner, Vanessa; Petrovcikova, Eva; Zahradnikova, Alexandra, Jr.; Vicikova, Kristina; Horejsi, Vaclav; Stockinger, Hannes; Leksa, Vladimir
Abstract
The plasminogen system is harnessed in a wide variety of physiological processes, such as fibrinolysis, cell migration, or efferocytosis; and accordingly, it is essential upon inflammation, tissue remodeling, wound healing, and for homeostatic maintenance in general. Previously, we identified a plasminogen receptor in the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R, CD222). Here, we demonstrate by means of genetic knockdown, knockout, and rescue approaches combined with functional studies that M6P/IGF2R is up-regulated on the surface of macrophages, recognizes plasminogen exposed on the surface of apoptotic cells, and mediates plasminogen-induced efferocytosis. The level of uptake of plasminogen-coated apoptotic cells inversely correlates with the TNF-alpha production by phagocytes indicating tissue clearance without inflammation by this mechanism. Our results reveal an up-to-now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.
The Function of Long Non-coding RNAs in Genomic Imprinting
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
Authors: Yang Wen-Zhi; Zhang Cui; Wang Guan-Nan; Li Dong-Jie; Li Shi-Jie
Abstract
Long noncoding RNAs (lncRNA) are non-protein coding transcripts longer than 200 nucleotides. The field of long noncoding RNA (lncRNA) research has been rapidly advancing in recent years as its large number and important biological functions. Genomic imprinting is an epigenetic phenomenon. The lncRNAs play a critical role in important biological functions by establishing genomic imprinting of target genes. Genomic imprinting has been a great resource for studying transcriptional and post-transcriptional-based gene regulation by lncRNAs. This review will focus on the mechanisms of imprinting in six of the most well-studied imprinted gene clusters: Kcnq1/Cdkn1c, Igf2r/Airn, Prader-Willi (PWS)/Angelman (AS), Snurf/Snrpn, Dlk1-Dio3, H19/Igf2, and overview the functional role of antisense lncRNAs (Kcnq1ot1t1, Airn and Ube3a-ATS), intergenic lncRNAs (H19, IPW and MEG3), and enhancer lncRNAs (IG-DMR eRNAs) to understand the diverse mechanisms being employed by them in cis and (/or) trans to regulate the parent-of-origin-specific expression of target genes. A better understanding of these downstream mechanisms will help to improve our general understanding of the function of ncRNAs throughout the genome.