LncRNA small nucleolar RNA host gene 16 reduces sepsis‐induced myocardial damage by regulating miR‐421/suppressor of cytokine signaling 5 axis

Abstract

Currently, sepsis‐induced cardiomyopathy (SIC) remains as one of the most critical clinical syndromes in terminally ill patients. Noncoding RNAs (including microRNAs and long noncoding RNAs) are implicated in both the onset and development of SIC. We herein investigated the functional role and molecular target of long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) in an in vitro SIC model of H9c2 myocardial cells. We used lipopolysaccharide (LPS) as endotoxin to treat H9c2 cells to mimic SIC damages. Cell Counting Kit 8 and apoptosis assay were performed to assess cell proliferation and cell death. Quantitative real‐time‐PCR and Western blot were employed to examine gene expression level at mRNA and protein level. Dual luciferase assay is used to validate the functional interactions between SNHG16/mi‐R421 and miR‐421/suppressor of cytokine signaling 5 (SOCS5). Inflammatory cytokines were measured by ELISA. Superoxide dismutase and malondialdehyde measurement was performed to assess oxidative stress, which was further confirmed by 2′,7′‐dichlorofluorescin diacetate staining. Our data demonstrated that in the LPS‐induced sepsis model of myocardial cells, SNHG16 overexpression downregulated the expression level of miR‐421, which sustained the expression of SOCS5 to alleviate the adverse effects of LPS, such as apoptosis, pro‐inflammatory cytokines, and oxidative stress. Our data suggest that SNHG16 functions as a ceRNA to maintain SOCS5 level by targeting miR‐421, thereby attenuating LPS‐induced myocardial cell damages. Targeting miR‐421 or modulating lncRNA SNHG16 level may be leveraged as a beneficial strategy against sepsis‐induced cellular damage in cardiomyocytes.

Sequential inspiratory muscle exercise-noninvasive positive pressure ventilation alleviates oxidative stress in COPD by mediating SOCS5/JAK2/STAT3 pathway

“…SOCS family proteins are a class of negative regulators of JAK2-STAT3 signaling pathway, consisting of SOCS1-7, both containing Src-homology domian and a conserved C-termial domain [ 46 ]. Among them, SOCS5 is expressed in a variety of adult tissues, playing anti-inflammatory, anti-tumor, anti-oxidative stress and other functions [ 16 , 47 , 48 ]. Xi et al uncovered that salidroside could promote SOCS5 transcription to reduce airway inflammation and airway remodeling in asthmatic mice [ 48 ].…”

“…A recent study showed that inhibiting SOCS5 significantly promoted cigarette extract-induced inflammatory responses, exacerbating COPD progression [ 17 ]. It also shown that maintaining SOCS5 expression could reduce LPS-induced oxidative stress and inflammation and improve myocardial injury [ 16 ]. Here, we established a COPD mouse model, whose results further verified that overexpression of SOCS5 inhibited JAK2/STAT3 pathway activation, improved lung function and reduced oxidative stress in COPD mice.…”

“…Suppressor of cytokine signaling 5 (SOCS5) is a main member of SOCS family, which are known to be cytokine-inducible negative regulators of cytokine signaling, also called as signal transducer and activator of transcription (STAT)-induced STAT inhibitor (SSI) protein family. A recent finding revealed that the maintain of SOCS5 could alleviate lipopolysaccharide-induced oxidative stress and the release of pro-cytokine factors to attenuate myocardial injury [ 16 ]. More importantly, Diao et al’s study also confirmed that downregulation of SOCS5 targeted by miR-132 could aggravate the inflammatory responses in COPD pathophysiology [ 17 ].…”