LncRNA MALAT1-deficiency restrains lipopolysaccharide (LPS)-induced pyroptotic cell death and inflammation in HK-2 cells by releasing microRNA-135b-5p

Journal of Immunology Research

Zhi

Lin

et al. 2022

Sepsis is a life-threatening organ dysfunction caused by the uncontrolled inflammation, easily affecting the kidney. Sepsis-induced acute kidney injury (S-AKI) has high morbidity and mortality, of which the pathophysiological mechanisms have not been completely illuminated, leading to nonspecific therapies. Specific microRNAs were related with the pathogenesis of AKI. However, only limited studies focused on the pyroptosis in the context of S-AKI. The in vitro LPS-induced HK-2 cell model and in vivo CLP-induced mouse model were established. qRT-PCR, Western blot, ELISA, and RNA pulldown were used for expression examination. Multiple biological databases were used for miRNA screening. H&E staining and IHC staining were performed. The LPS-induced HK-2 cells showed significantly increased ( P < 0.01 ) fluorescence intensity of N-GSDMD and ASC compared with the HK-2 cells. The expression of NLRP3, NEK7, ASC, active caspase-1, and N-GSDMD was significantly enhanced ( P < 0.05 ) and the inflammatory factors including IL-18, IL-1β, and THF-α were all increased in LPS-induced HK-2 cells and CLP-induced mice. Renal edema, serum Cr and BUN, and expression of KIM-1 and NGAL were significantly higher ( P < 0.05 ) in CLP-induced S-AKI mice than the sham group. miR-101-3p, miR-144-3p, miR-181a-5p, miR-4262, and miR-513b-5p could inhibit NEK7. NEK7 is an interacting protein of miRNA-181a-5p. miR-181a-5p inhibits pyroptosis of the LPS-induced HK-2 cells through downregulation of NEK7. Pyroptosis of HK-2 cells promotes inflammation. miR-181a-5p inhibits pyroptosis through downregulation of NEK7 in LPS-induced HK-2 cells and CLP-induced mice. Our study indicated miR-181a-5p as a new potential therapeutic target for S-AKI therapy.

Section: Discussionmentioning

confidence: 99%

miR-181a-5p Inhibits Pyroptosis in Sepsis-Induced Acute Kidney Injury through Downregulation of NEK7

Journal of Immunology Research

Zhi

Lin

et al. 2022

“…LncRNA MALAT1 attenuates renal injury by acting as an RNA sponge for miRNA-135b-5p to regulate NLRP3, which is involved in regulating pyroptosis. [ 47 ] LncRNA MALAT1 can also regulate miR-23c targeting ELAVL1 in DN to regulate renal tubular epithelial cell pyroptosis. [ 48 ] LncRNA-ANRIL with spongy effects can directly target miR-497 to promote NLRP3 inflammatory vesicle activation and promote pyroptosis during DN.…”

Section: Microrna Crosstalk With Pcd In Renal Diseases and Clinical A...mentioning

confidence: 99%

Role of microRNAs in programmed cell death in renal diseases: A review

Chen

et al. 2023

Medicine

MicroRNAs (miRNAs) regulate gene expression involving kidney morphogenesis and cell proliferation, apoptosis, differentiation, migration, invasion, immune evasion, and extracellular matrix remodeling. Programmed cell death (PCD) is mediated and regulated by specific genes and a wealth of miRNAs, which participate in various pathological processes. Dysregulation of miRNAs can disrupt renal development and induce the onset and progression of various renal diseases. An in-depth understanding of how miRNAs regulate renal development and diseases is indispensable to comprehending how they can be used in new diagnostic and therapeutic approaches. However, the mechanisms are still insufficiently investigated. Hence, we review the current roles of miRNA-related signaling pathways and recent advances in PCD research and aim to display the potential crosstalk between miRNAs and PCD. The prospects of miRNAs as novel biomarkers and therapeutic targets are also described, which might provide some novel ideas for further studies.

“…Maternally expressed gene three controls gasdermin D expression by acting as a ceRNA of miR-18a-3p to promote tubular epithelial cell pyroptosis ( Deng J. et al, 2021 ). Other lncRNAs, such as lncRNA DLX6 antisense RNA 1, MALAT1, PVT1, and GAS5, are involved in pyroptosis in sepsis-associated renal injury ( Tan et al, 2020 ; Deng L. T. et al, 2021 ; Huang and Xu, 2021 ; Ling et al, 2021 ). Resveratrol rescues the viability and cytokine release of LPS-treated HK2 cells by inactivating the lncRNA MALAT1/miR-205 axis and attenuates sepsis-induced AKI ( Wang B. et al, 2021 ).…”

Section: Lncrna and Akimentioning

confidence: 99%

Kidney diseases and long non-coding RNAs in the limelight

Liu

et al. 2022

Front. Physiol.

The most extensively and well-investigated sequences in the human genome are protein-coding genes, while large numbers of non-coding sequences exist in the human body and are even more diverse with more potential roles than coding sequences. With the unveiling of non-coding RNA research, long-stranded non-coding RNAs (lncRNAs), a class of transcripts >200 nucleotides in length primarily expressed in the nucleus and rarely in the cytoplasm, have drawn our attention. LncRNAs are involved in various levels of gene regulatory processes, including but not limited to promoter activity, epigenetics, translation and transcription efficiency, and intracellular transport. They are also dysregulated in various pathophysiological processes, especially in diseases and cancers involving genomic imprinting. In recent years, numerous studies have linked lncRNAs to the pathophysiology of various kidney diseases. This review summarizes the molecular mechanisms involved in lncRNAs, their impact on kidney diseases, and associated complications, as well as the value of lncRNAs as emerging biomarkers for the prevention and prognosis of kidney diseases, suggesting their potential as new therapeutic tools.