Long Non-Coding RNAs in Cardiac and Pulmonary Fibroblasts and Fibrosis

The cardiopulmonary system delivers oxygen throughout the body via blood circulation. It is an essential part of the body to sustain the lives of organisms. The integral parts of the cardiopulmonary system—the heart and lungs—are constantly exposed to damaging agents (e.g., dust, viruses), and can be greatly affected by injuries caused by dysfunction in tissues (e.g., myocardial infarction). When damaged, mesenchymal cells, such as fibroblasts, are activated to become myofibroblasts to initiate fibrosis as part of a regenerative mechanism. In diseased states, the excess accumulation of extracellular matrices secreted by myofibroblasts results in further dysfunction in the damaged organs. These fibrotic tissues cannot easily be removed. Thus, there is a growing interest in understanding the fibrotic process, as well as finding biomolecules that can be targets for slowing down or potentially stopping fibrosis. Among these biomolecules, the interest in studying long non-coding RNAs (lncRNAs; any non-protein-coding RNAs longer than 200 nucleotides) has intensified in recent years. In this commentary, we summarize the current status of lncRNA research in the cardiopulmonary system by focusing on cardiac and pulmonary fibrosis

Artemin and an Artemin-Derived Peptide, Artefin, Induce Neuronal Survival, and Differentiation Through Ret and NCAM

Artemin (ARTN) is a neurotrophic factor from the GDNF family ligands (GFLs) that is involved in development of the nervous system and neuronal differentiation and survival. ARTN signals through a complex receptor system consisting of the RET receptor tyrosine kinase and a glycosylphosphatidylinositol-anchored co-receptor GFL receptor α, GFRα3. We found that ARTN binds directly to neural cell adhesion molecule (NCAM) and that ARTN-induced neuritogenesis requires NCAM expression and activation of NCAM-associated signaling partners, thus corroborating that NCAM is an alternative receptor for ARTN. We designed a small peptide, artefin, that could interact with GFRα3 and demonstrated that this peptide agonist induces RET phosphorylation and mimics the biological functions of ARTN – neuroprotection and neurite outgrowth. Moreover, artefin mimicked the binding of ARTN to NCAM and required NCAM expression and activation for its neurite elongation effect, thereby suggesting that artefin represents a binding site for NCAM within ARTN. We showed that biological effects of ARTN and artefin can be inhibited by abrogation of both NCAM and RET, suggesting a more complex signaling mechanism that previously thought. As NCAM plays a significant role in neurodevelopment, regeneration, and synaptic plasticity we suggest that ARTN and its mimetics are promising candidates for treatment of neurological disorders and warrant further investigations

The current status of gene expression profilings in COVID-19 patients

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has swept through every part of the world. Because of its impact, international efforts have been underway to identify the variants of SARS‐CoV‐2 by genome sequencing and to understand the gene expression changes in COVID‐19 patients compared to healthy donors using RNA sequencing (RNA‐seq) assay. Within the last two and half years since the emergence of SARS‐CoV‐2, a large number of OMICS data of COVID‐19 patients have accumulated. Yet, we are still far from understanding the disease mechanism. Further, many people suffer from long‐term effects of COVID‐19; calling for a more systematic way to data mine the generated OMICS data, especially RNA‐seq data. METHODS: By searching gene expression omnibus (GEO) using the key terms, COVID‐19 and RNA‐seq, 108 GEO entries were identified. Each of these studies was manually examined to categorize the studies into bulk or single‐cell RNA‐seq (scRNA‐seq) followed by an inspection of their original articles. RESULTS: The currently available RNA‐seq data were generated from various types of patients’ samples, and COVID‐19 related sample materials have been sequenced at the level of RNA, including whole blood, different components of blood [e.g., plasma, peripheral blood mononuclear cells (PBMCs), leukocytes, lymphocytes, monocytes, T cells], nasal swabs, and autopsy samples (e.g., lung, heart, liver, kidney). Of these, RNA‐seq studies using whole blood, PBMCs, nasal swabs and autopsy/biopsy samples were reviewed to highlight the major findings from RNA‐seq data analysis. CONCLUSIONS: Based on the bulk and scRNA‐seq data analysis, severe COVID‐19 patients display shifts in cell populations, especially those of leukocytes and monocytes, possibly leading to cytokine storms and immune silence. These RNA‐seq data form the foundation for further gene expression analysis using samples from individuals suffering from long COVID