RGD Reference Report - LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis. - Rat Genome Database

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LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis.

Authors: Wang, Sixuan  Duan, Jun  Liao, Jiangquan  Wang, Yan  Xiao, Xiang  Li, Lin  Liu, Yi  Gu, Huan  Yang, Peng  Fu, Dongliang  Du, Jinhang  Li, Xianlun  Shao, Mingjing 
Citation: Wang S, etal., Aging (Albany NY). 2022 Aug 30;14(16):6809-6828. doi: 10.18632/aging.204256. Epub 2022 Aug 30.
RGD ID: 156430337
Pubmed: PMID:36044268   (View Abstract at PubMed)
PMCID: PMC9467416   (View Article at PubMed Central)
DOI: DOI:10.18632/aging.204256   (Journal Full-text)


OBJECTIVE: Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis.
METHODS: C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected.
RESULTS: H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosis in vivo. H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosis in vitro. Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT).
CONCLUSION: H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKT1HumanDiabetic Cardiomyopathies amelioratesISOAkt1 (Mus musculus) RGD 
ATF6HumanDiabetic Cardiomyopathies amelioratesISOAtf6 (Mus musculus) RGD 
Akt1MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
Akt1RatDiabetic Cardiomyopathies amelioratesISOAkt1 (Mus musculus) RGD 
Atf6MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
Atf6RatDiabetic Cardiomyopathies amelioratesISOAtf6 (Mus musculus) RGD 
BAXHumanDiabetic Cardiomyopathies amelioratesISOBax (Mus musculus) RGD 
BaxRatDiabetic Cardiomyopathies amelioratesISOBax (Mus musculus) RGD 
BaxMouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
DDIT3HumanDiabetic Cardiomyopathies amelioratesISODdit3 (Mus musculus) RGD 
Ddit3MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
Ddit3RatDiabetic Cardiomyopathies amelioratesISODdit3 (Mus musculus) RGD 
H19RatDiabetic Cardiomyopathies amelioratesISOH19 (Mus musculus) RGD 
H19HumanDiabetic Cardiomyopathies amelioratesISOH19 (Mus musculus) RGD 
H19MouseDiabetic Cardiomyopathies amelioratesIMP  RGD 
HSP90B1HumanDiabetic Cardiomyopathies amelioratesISOHsp90b1 (Mus musculus) RGD 
HSPA5HumanDiabetic Cardiomyopathies amelioratesISOHspa5 (Mus musculus) RGD 
Hsp90b1MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
Hsp90b1RatDiabetic Cardiomyopathies amelioratesISOHsp90b1 (Mus musculus) RGD 
Hspa5RatDiabetic Cardiomyopathies amelioratesISOHspa5 (Mus musculus) RGD 
Hspa5MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
MIR140HumanDiabetic Cardiomyopathies amelioratesISOMir140 (Mus musculus) RGD 
MTORHumanDiabetic Cardiomyopathies amelioratesISOMtor (Mus musculus) RGD 
Mir140RatDiabetic Cardiomyopathies amelioratesISOMir140 (Mus musculus) RGD 
Mir140MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
MtorRatDiabetic Cardiomyopathies amelioratesISOMtor (Mus musculus) RGD 
MtorMouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
NFE2L2HumanDiabetic Cardiomyopathies amelioratesISONfe2l2 (Mus musculus) RGD 
Nfe2l2MouseDiabetic Cardiomyopathies amelioratesIEP  RGD 
Nfe2l2RatDiabetic Cardiomyopathies amelioratesISONfe2l2 (Mus musculus) RGD 
PIK3CAHumanDiabetic Cardiomyopathies amelioratesISOPik3ca (Mus musculus) RGD 
Pik3caRatDiabetic Cardiomyopathies amelioratesISOPik3ca (Mus musculus) RGD 
Pik3caMouseDiabetic Cardiomyopathies amelioratesIEP  RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKT1Humanstreptozocin increases phosphorylationISOAkt1 (Mus musculus)streptozocin increases phosphorylation of Akt1 protein in heartRGD 
ATF6Humanstreptozocin increases expression ISOAtf6 (Mus musculus)streptozocin increases expression of Atf6 protein in heartRGD 
Akt1Ratstreptozocin increases phosphorylationISOAkt1 (Mus musculus)streptozocin increases phosphorylation of Akt1 protein in heartRGD 
Akt1Mousestreptozocin increases phosphorylationEXP streptozocin increases phosphorylation of Akt1 protein in heartRGD 
Atf6Ratstreptozocin increases expression ISOAtf6 (Mus musculus)streptozocin increases expression of Atf6 protein in heartRGD 
Atf6Mousestreptozocin increases expression EXP streptozocin increases expression of Atf6 protein in heartRGD 
DDIT3Humanstreptozocin increases expression ISODdit3 (Mus musculus)streptozocin increases expression of Ddit3 protein in heartRGD 
Ddit3Ratstreptozocin increases expression ISODdit3 (Mus musculus)streptozocin increases expression of Ddit3 protein in heartRGD 
Ddit3Mousestreptozocin increases expression EXP streptozocin increases expression of Ddit3 protein in heartRGD 
EIF2AK3Humanstreptozocin increases phosphorylationISOEif2ak3 (Mus musculus)streptozocin increases phosphorylation of Eif2ak3 protein in heartRGD 
Eif2ak3Mousestreptozocin increases phosphorylationEXP streptozocin increases phosphorylation of Eif2ak3 protein in heartRGD 
HSP90B1Humanstreptozocin increases expression ISOHsp90b1 (Mus musculus)streptozocin increases expression of Hsp90b1 protein in heartRGD 
HSPA5Humanstreptozocin increases expression ISOHspa5 (Mus musculus)streptozocin increases expression of Hspa5 protein in heartRGD 
Hsp90b1Ratstreptozocin increases expression ISOHsp90b1 (Mus musculus)streptozocin increases expression of Hsp90b1 protein in heartRGD 
Hsp90b1Mousestreptozocin increases expression EXP streptozocin increases expression of Hsp90b1 protein in heartRGD 
Hspa5Ratstreptozocin increases expression ISOHspa5 (Mus musculus)streptozocin increases expression of Hspa5 protein in heartRGD 
Hspa5Mousestreptozocin increases expression EXP streptozocin increases expression of Hspa5 protein in heartRGD 
MIR140Humanstreptozocin increases expressionISOMir140 (Mus musculus)streptozocin increases expression of Mir140 RNA in heartRGD 
MTORHumanstreptozocin increases phosphorylationISOMtor (Mus musculus)streptozocin increases increases phosphorylation of Mtor protein in heartRGD 
Mir140Mousestreptozocin increases expressionEXP streptozocin increases expression of Mir140 RNA in heartRGD 
Mir140Ratstreptozocin increases expressionISOMir140 (Mus musculus)streptozocin increases expression of Mir140 RNA in heartRGD 
MtorRatstreptozocin increases phosphorylationISOMtor (Mus musculus)streptozocin increases increases phosphorylation of Mtor protein in heartRGD 
MtorMousestreptozocin increases phosphorylationEXP streptozocin increases increases phosphorylation of Mtor protein in heartRGD 
NFE2L2Humanstreptozocin increases expression ISONfe2l2 (Mus musculus)streptozocin increases expression of Nfe2l2 protein in heartRGD 
Nfe2l2Ratstreptozocin increases expression ISONfe2l2 (Mus musculus)streptozocin increases expression of Nfe2l2 protein in heartRGD 
Nfe2l2Mousestreptozocin increases expression EXP streptozocin increases expression of Nfe2l2 protein in heartRGD 
PIK3CAHumanstreptozocin multiple interactionsISOPik3ca (Mus musculus)streptozocin decreases expression and increases phosphorylation of Pik3ca in cardiac muscle cellsRGD 
Pik3caRatstreptozocin multiple interactionsISOPik3ca (Mus musculus)streptozocin decreases expression and increases phosphorylation of Pik3ca in cardiac muscle cellsRGD 
Pik3caMousestreptozocin multiple interactionsEXP streptozocin decreases expression and increases phosphorylation of Pik3ca in cardiac muscle cellsRGD 
DDIT3Humanthapsigargin multiple interactionsISODdit3 (Mus musculus)thapsigargin promotes the reaction [glucose increases expression of Ddit3 protein in cardiac muscle cell]RGD 
Ddit3Mousethapsigargin multiple interactionsEXP thapsigargin promotes the reaction [glucose increases expression of Ddit3 protein in cardiac muscle cell]RGD 
Ddit3Ratthapsigargin multiple interactionsISODdit3 (Mus musculus)thapsigargin promotes the reaction [glucose increases expression of Ddit3 protein in cardiac muscle cell]RGD 
EIF2AK3Humanthapsigargin multiple interactionsEXP glucose promotes the reaction [thapsigargin increases phosphorylation of Eif2ak3 protein in cardiac muscle cells]RGD 
Eif2ak3Mousethapsigargin multiple interactionsISOEIF2AK3 (Homo sapiens)glucose promotes the reaction [thapsigargin increases phosphorylation of Eif2ak3 protein in cardiac muscle cells]RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Atf6  (activating transcription factor 6)
Bax  (BCL2 associated X, apoptosis regulator)
Ddit3  (DNA-damage inducible transcript 3)
H19  (H19 imprinted maternally expressed transcript)
Hsp90b1  (heat shock protein 90 beta family member 1)
Hspa5  (heat shock protein family A (Hsp70) member 5)
Mir140  (microRNA 140)
Mtor  (mechanistic target of rapamycin kinase)
Nfe2l2  (NFE2 like bZIP transcription factor 2)
Pik3ca  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)
Atf6  (activating transcription factor 6)
Bax  (BCL2-associated X protein)
Ddit3  (DNA-damage inducible transcript 3)
Eif2ak3  (eukaryotic translation initiation factor 2 alpha kinase 3)
H19  (H19, imprinted maternally expressed transcript)
Hsp90b1  (heat shock protein 90, beta (Grp94), member 1)
Hspa5  (heat shock protein 5)
Mir140  (microRNA 140)
Mtor  (mechanistic target of rapamycin kinase)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)
Pik3ca  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)
ATF6  (activating transcription factor 6)
BAX  (BCL2 associated X, apoptosis regulator)
DDIT3  (DNA damage inducible transcript 3)
EIF2AK3  (eukaryotic translation initiation factor 2 alpha kinase 3)
H19  (H19 imprinted maternally expressed transcript)
HSP90B1  (heat shock protein 90 beta family member 1)
HSPA5  (heat shock protein family A (Hsp70) member 5)
MIR140  (microRNA 140)
MTOR  (mechanistic target of rapamycin kinase)
NFE2L2  (NFE2 like bZIP transcription factor 2)
PIK3CA  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)


Additional Information