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Notes: Summary: Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is encoded by the mitogen-inducible gene 3CH 134. MKP-1 has recently been shown to be a dual specificity (serine/threonine, tyrosine) protein phosphatase, which dephosphorylates and inactivates MAP kinases in vitro and in vivo. to seek the role of MKP-1 in growth regulation of mesangial cells, expression of MKP-1 mRNA in cultured mesangial cells and in glomeruli isolated from anti-Thy 1.1 mesangial proliferative glomerulonephritis rats was studied. the effect of inhibition of endogenous MKP-1 by use of antisense-DNA technology on the regulation of MAP kinase activity and the growth regulation of rat cultured inesangial cells was also studied. By northern blot analysis, it was demonstrated that in mesangial cells, MKP-1 mRNA expression was rapidly induced after the stimulation by serum, growth factors and vasoactive peptides. Maximal signals were found in 30-60 min in all growth factors tested. Fetal calf serum (FCS) was the most potent stimulus of MKP-1 mRNA expression, followed by platelet-derived growth factor (PDGF)-B and arginine vasopressin. to elucidate a possible involvement of MKP-1 in disease development of mesangial proliferative glomerulonephritis, MKP-1 mRNA expression was examined in rat anti-Thy 1.1 glomerulonephritis model. A marked increase in MKP-1 mRNA level in isolated glomeruli was observed at day 3 after disease induction (4.3-fold over control). In situ hybridization of MKP-1 mRNA in Thy 1.1 glomerulonephritius rats confirmed the enhanced glomerular expression of MKP-1. to study the role of MKP-1 in mesangial cell growth regulation, phosphorothioate oligodeoxynucleotide (ODN) were used to modulate MKP-1 expression. an antisense ODN targeting the translation initiation site of MKP-1 mRNA inhibited stimulated (by FCS, or PDGF-B) DNA synthesis and FCS- or PDGF-induced mitogenesis in mesangial cells. Sense ODN or mismatched ODN had no effect on the DNA synthesis or mitogenic response of mesangial cells. These results suggest that MKP-1 is an immediately early gene in rat mesangial cells and it plays a critical role in growth regulation of mesangial cells in vitro.

Notes: Summary: The renin-angiotension system (RAS) component gene polymorphisms was examined in 216 patients undergoing maintenance haemodialysis (HD) therapy and in 208 control subjects. the RAS polymorphisms selected for analysis were angiotensin I converting enzyme (ACE) I/D, angiotensinogen (Agt) T235/M235, angiotensin II type 1 receptor (AGT1R) A1166/C1166. the control allelic frequencies was ACE I/D (0.63/0.37), Agt T235/M235 (0.16/0.84), and AGT1R A1166/C1166 (0.94/0.06). Recently, relationships between ACE I/D and the progression of renal disease attract great attention in Japanese and Caucasian populations. ACE D allele was expected to be more frequent in HD population. However, no accumulation of ACE D allele or Agt T235 allele, AFT1R C1166 allele in Japanese end-stage renal disease (ESRD) subjects was detected. to explain the paradoxical result of positive association of ACE D allele with progression of renal disease and no bias of ACE genotype in ESRD subjects, further investigation with systematic prospective study regarding the change of ACE genotype distribution around the period of entering dialysis therapy is required.