Histone Deacetylases Take Center Stage on Regulation of Podocyte Function

Abstract

Background: Podocytes (highly specialized and terminally differentiated epithelial cells) are integral components of the glomerular filtration barrier that are vulnerable to a variety of injuries and, as a result, they undergo a series of changes ranging from hypertrophy to detachment and apoptosis. Podocyte injury is a major determinant in proteinuric kidney disease and identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Although numerous studies have achieved dramatic advances in the understanding of podocyte biology and its relevance to renal injury, few effective and specific therapies are available. Summary: Epigenetic modifications have been proven to play important roles in the pathogenesis of kidney diseases. Among them, histone deacetylase (HDAC)-mediated epigenetic acetylation in the kidney has attracted much attention, which may play multiple roles in both kidney development and the pathogenesis of kidney disease. Recent studies have demonstrated that HDAC protect against podocyte injury by regulation of inflammation, apoptosis, autophagy, mitochondrial function, and insulin resistance. In this review, we summarize recent advances in the understanding of the functions and regulatory mechanisms of HDAC in podocytes and associated proteinuric kidney diseases. In addition, we provide evidence of the potential therapeutic effects of HDAC inhibitors for proteinuric kidney disease. Key Messages: Pharmacological targeting of HDAC-mediated epigenetic processes may open new therapeutic avenues for chronic kidney disease.

Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome

“…Paecilomyces cicadae-fermented Radix astragali can enhance the autophagy of podocytes induced by high glucose, enhance cell viability, and reduce apoptosis [25]. Histone deacetylase protects podocytes from damage by regulating inflammation, autophagy, and insulin resistance [26]. Hepatocyte growth factor regulates the PI3K/Akt-GSK3 sh-TFEB axis and protects diabetic nephropathy through the podocyte autophagy-lysosome pathway [27].…”

Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury

“…The majority of patients with NS need to conceive daily treatment with corticosteroids until complete remission of proteinuria ( 16 ), side effects of corticosteroids are concerned, which promote us to explore potential drugs for alternative therapeutic intervention. HDAC inhibitors exhibited beneficial impacts against podocyte injury and proteinuria ( 17 ). HDAC IIa composes of HDAC4, HDAC5, HDAC7, and HDAC9, numbers of studies demonstrated HDAC IIa inhibition as an alternative approach to avoid the progression of various diseases, examples like breast tumors ( 18 ), pancreatic cancer ( 19 ), multiple myeloma ( 20 ), and type 2 diabetes ( 21 ).…”