RESUMO
Objective To investigate the effects of 12-lipoxygenase (12-LO) and angiotensin Ⅱ (Ang Ⅱ) on the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) p21,p27 and p57 related to cell hypertrophy.Methods Mesangial cells were treated with high glucose for 24 hours and 48 hours respectively.12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and Ang Ⅱ were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed high fat diet were received low dose streptozotocin (STZ) to make type 2 diabetes (DN).The rats were divided into normal control group,DN group,DN+Ang Ⅱ type 1 receptor blocker (ARB) group or 12-LO inhibitor (CDC) group.DN+ARB rats were treated by losartan for 6 weeks,and DN+CDC rats were treated for 8 weeks.Urine albumin and protein expressions of p21,p27 and p57 were detected by ELISA and Western blotting respectively.Glomeruli injury and expressions of p21 and p27 were detected by PAS staining and immunohistochemistry respectively.Results High glucose increased p21 and p27 protein expression in mesangial cells significantly compared with the relative control (all P ＜ 0.05),but had no effect on p57.Ang Ⅱ increased p27 protein expression in gloneruli significantly (P ＜ 0.05),but had no effect on p21 and p57 protein expression.12(S)-HETE increased both p21 and p27 protein expression in glomeruli significantly (all P ＜ 0.05),but had no effect on p57 protein expression.Blood glucose,kidney/body weight,urinary protein,and glomerular p21 and p27 protein expressions were increased in DN group (all P ＜ 0.05) compared with those in control group,with little change of p57 protein expression (P ＜ 0.05).Moreover,glomerular hypertrophy and extra cellular matrix accumulation were observed in DN group.However,urine protein,kidney/body weight,renal injury,but not blood glucose,were decreased in DN+ARB group and DN+CDC group compared with DN group respectively (P＜ 0.05).Further DN+CDC rats had decreased both p21 and p27 protein expressions in glomeruli,but DN+ ARB rats only had decreased p27 protein expression (all P ＜ 0.05).Conclusions 12-LO may induce both p21 and p27 protein expression in DN glomeruli,but Ang Ⅱ may induce only p27 expression.
RESUMO
BACKGROUND AND OBJECTIVES: We determined the localization of leukocyte-type 12-lipoxygenase (L-12-LO) in murine nasal mucosa and to investigate the expression of L-12-LO according to the development of murine nasal mucosa. MATERIALS AND METHOD: Immunohistochemical staining was done on the nasal mucosa of mice at gestational days 16, 17, 18, and mice at postnatal days 1, 3, 7, 14, and adult mice. Alcian blue (pH 2.5)-periodic acid Schiff staining on murine nasal mucosa was performed. RESULTS: In murine nasal respiratory mucosa, the expression of L-12-LO was noted in ciliated epithelial cells, basal cells, serous acini, and secretory ducts, but it was not found in the mucous acini and goblet cells. In olfactory mucosa, the expression of L-12-LO was noted in the olfactory receptor cells, supporting cells, and basal cells. The expression in respiratory mucosa according to the development was strongly noticed from the gestational day 16 through postnatal day 7. The expression in postnatal day 14 and adult mice was weaker than in the previous time point. The expression in olfactory mucosa showed no difference throughout the developmental stage. CONCLUSION: As a result of this study, we found the exact localization of L-12-LO in murine nasal mucosa, and we also found the different expression of L-12-LO between the respiratory and olfactory mucosa. This fact suggests the possible involvement of L-12-LO in the development of murine respiratory mucosa.