Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity.

Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = -0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases.

Targeting glia for bone cancer pain.

INTRODUCTION: Bone cancer pain (BCP) remains to be a clinical challenge with limited pharmaceutical interventions. Therefore, novel therapeutic targets for the management of BCP are in desperate need. Recently, a growing body of evidence has suggested that glial cells may play a pivotal role in the pathogenesis of BCP. Areas covered: This review summarizes the recent progress in the understanding of glia in BCP and reveals the potential therapeutic targets in glia for BCP treatment. Expert opinion: Pharmacological interventions inhibiting the activation of glial cells, suppressing glia-derived proinflammatory cytokines, cell surface receptors, and the intracellular signaling pathways may be beneficial for the pain management of advanced cancer patients. However, these pharmacological interventions should not disrupt the normal function of glia cells since they play a vital supportive and protective role in the central nervous system.