RGD Reference Report - Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. - Rat Genome Database

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Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy.

Authors: Wang, X  Liu, J  Zhen, J  Zhang, C  Wan, Q  Liu, G  Wei, X  Zhang, Y  Wang, Z  Han, H  Xu, H  Bao, C  Song, Z  Zhang, X  Li, N  Yi, F 
Citation: Wang X, etal., Kidney Int. 2014 Oct;86(4):712-25. doi: 10.1038/ki.2014.111. Epub 2014 Apr 9.
RGD ID: 9590311
Pubmed: PMID:24717296   (View Abstract at PubMed)
DOI: DOI:10.1038/ki.2014.111   (Journal Full-text)

Studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of diabetic complications. Inhibitors of HDAC are a novel class of therapeutic agents in diabetic nephropathy, but currently available inhibitors are mostly nonselective inhibit multiple HDACs, and different HDACs serve very distinct functions. Therefore, it is essential to determine the role of individual HDACs in diabetic nephropathy and develop HDAC inhibitors with improved specificity. First, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC2/4/5 were upregulated in the kidney from streptozotocin-induced diabetic rats, diabetic db/db mice, and in kidney biopsies from diabetic patients. Podocytes treated with high glucose, advanced glycation end products, or transforming growth factor-beta (common detrimental factors in diabetic nephropathy) selectively increased HDAC4 expression. The role of HDAC4 was evaluated by in vivo gene silencing by intrarenal lentiviral gene delivery and found to reduce renal injury in diabetic rats. Podocyte injury was associated with suppressing autophagy and exacerbating inflammation by HDAC4-STAT1 signaling in vitro. Thus, HDAC4 contributes to podocyte injury and is one of critical components of a signal transduction pathway that links renal injury to autophagy in diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies  ISOHdac2 (Mus musculus)9590311; 9590311protein:increased expression:kidney:RGD 
Diabetic Nephropathies  IEP 9590311; 9590311; 9590311; 9590311; 9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHdac2 (Rattus norvegicus)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies treatmentISOHdac4 (Rattus norvegicus)9590311; 9590311 RGD 
Diabetic Nephropathies  ISOHdac4 (Rattus norvegicus)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHdac4 (Mus musculus)9590311; 9590311protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHdac5 (Mus musculus)9590311; 9590311protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHdac5 (Rattus norvegicus)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHDAC2 (Homo sapiens)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies  IEP 9590311; 9590311; 9590311protein:increased expression:kidney:RGD 
Diabetic Nephropathies treatmentIMP 9590311 RGD 
Diabetic Nephropathies  ISOHDAC4 (Homo sapiens)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 
Diabetic Nephropathies  ISOHDAC5 (Homo sapiens)9590311; 9590311mRNA and protein:increased expression:kidney:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdac2  (histone deacetylase 2)
Hdac4  (histone deacetylase 4)
Hdac5  (histone deacetylase 5)

Genes (Mus musculus)
Hdac2  (histone deacetylase 2)
Hdac4  (histone deacetylase 4)
Hdac5  (histone deacetylase 5)

Genes (Homo sapiens)
HDAC2  (histone deacetylase 2)
HDAC4  (histone deacetylase 4)
HDAC5  (histone deacetylase 5)


Additional Information