Stem Cell-Derived Exosomes Prevent Aging-Induced Cardiac Dysfunction through a Novel Exosome/lncRNA MALAT1/NF-κB/TNF-α Signaling Pathway

Abstract

Aging is a risk factor for cardiovascular disease, and there is no effective therapeutic approach to alleviate this condition. NF-κB and TNF-α have been implicated in the activation of the aging process, but the signaling molecules responsible for the inactivation of NF-κB and TNF-α remain unknown. Exosomes have been reported to improve heart functions by releasing miRNA. Recent studies suggest that lncRNAs are more tissue-specific and developmental stage-specific compared to miRNA. However, the role of lncRNA in exosome-mediated cardiac repair has not been explored. In the present study, we focused on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which is an lncRNA associated with cell senescence. We discovered that human umbilical cord mesenchymal stem cell- (UMSC-) derived exosomes prevent aging-induced cardiac dysfunction. Silencer RNA against lncRNA MALAT1 blocked the beneficial effects of exosomes. In summary, we discovered that UMSC-derived exosomes prevent aging-induced cardiac dysfunction by releasing novel lncRNA MALAT1, which in turn inhibits the NF-κB/TNF-α signaling pathway. These findings will lead to the development of therapies that delay aging and progression of age-related diseases.

A Landscape of Murine Long Non-Coding RNAs Reveals the Leading Transcriptome Alterations in Adipose Tissue during Aging

“…As expected, the AR-lncRNAs, compared with aging-non-regulated lncRNAs (ANR-lncRNAs), showed a stronger correlation with aging course ( Figure S2A ), and were more dynamically expressed during aging in all 11 examined organs ( Figures S2B and S2C ). A few previously reported AR-lncRNAs such as H19 ( Hofmann et al, 2019 ), Malat1 ( Zhu et al, 2019 ), and Neat1 ( White et al, 2015 ) were identified in our AR-lncRNA list, attesting to the validity of our data analysis ( Table S2 ). Notably, the two WAT depots (eWAT and iWAT) had the highest number of AR-lncRNAs among all examined organs ( Figure 2A ; Table S2 ).…”

The role of lncRNA MALAT1 in cardiovascular disease

“…16 In addition, human umbilical cord mesenchymal stem cell secreted the exosomes containing MALAT1, which prevent aging-induced cardiac dysfunction via inhibition of NF-κB/TNF-α signaling pathway. 86 Similarly, MALAT1 induced by HBO in HCAECs and HCAECs-derived exosomes could promote angiogenesis via inhibition of miR-92, then up-regulation of KLF2. 57 6 | CONCLUSIONS CVD is the first leading cause of death.…”

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

“…found that exosomes released from human umbilical cord MSCs contain MALAT1, which was shown to inhibit the NF-κB/TNF-α pathway in cardiac inflammation. 51 In a similar vein, Sun et al…”