Hao‐Ai Shui

Autoimmune crescentic glomerulonephritis is characterized by severe immune response with glomerular crescentic formation and fibrosis in the kidney. Recent studies indicate that overexpression of renal Smad7 attenuates both renal fibrosis and inflammation in rat remnant kidney. However, little attention has been paid to the potential role of TGF-beta/Smad signaling in autoimmune kidney disease. This study tested the hypothesis that blocking TGF-beta signaling by overexpression of Smad7 may have a therapeutic effect in a mouse model of autoimmune crescentic glomerulonephritis that was induced in C57BL/6 x DBA/2J F1 hybrid mice by giving DBA/2J donor lymphocytes. Smad7 gene was transfected into the kidney using the ultrasound-microbubble-mediated system. Results showed that overexpression of Smad7 blocked both renal fibrosis and inflammatory pathways in terms of Smad2/3 and NF-kappaB activation (P < 0.01), thereby inhibiting alpha-smooth muscle actin; collagen I, III, and IV accumulation; and expression of inflammatory cytokines (IL-1beta and IL-6), adhesion molecule/chemokine (intercellular adhesion molecule-1, monocyte chemoattractant protein-1), and inducible nitric oxide synthase (all P < 0.01). Leukocyte infiltration (CD4(+) cells and macrophages) was also suppressed (P < 0.005). Severe histologic damage (glomerular crescent formation and tubulointerstitial injury) and functional injury including proteinuria were significantly improved (all P < 0.05). This study provides important evidence that overexpression of Smad7 may have therapeutic potential for autoimmune kidney disease.

The majority of male infertility results from poor sperm motility. A direct link between altered protein phosphorylation and aberrant sperm motility has not been established. To address this issue, sperm samples obtained from 20 donors with healthy sperm and 20 donors with aberrantly motile sperm were subjected to computer assisted semen analysis (CASA), proteomic analysis, Western blot, and immunofluorescent staining. Proteomic analysis identified 12 protein spots as having differential phosphorylation, including gamma-tubulin complex associated protein 2 (GCP2). Western blot and immunofluorescence demonstrated differential expression of gamma-tubulin between healthy and aberrantly motile sperm. In conclusion, hypophosphorylated proteins and reduced expression of gamma-tubulin may be associated with low motility sperm.