Expression and functional analysis of novel gene AngRem104 associated with glomerular sclerosis

AIM:To study the expression and function of novel gene AngRem104.METHODS:Northern blot was performed to detect the distribution of AngRem104 in human multiple normal tissues as well as the effect of AngⅡ and AT1R antagonist (losartan) on AngRem104 expression. The sense and antisense eukaryotic expression vectors of AngRem104 were constructed and transfected into human mesangial cells. RT-PCR was used to detect the expression of FN when AngRem104 was over-expressed. Primary sequence and motif analysis of AngRem104 protein were performed by on-line ExPasy predictive tools.RESULTS:AngRem104 was predicted to localize at the cellular nucleus. It was widely expressed in human heart, placenta, liver, muscle, kidney and pancreas. Moreover, the up-regulated expression of AngRem104 induced by AngⅡ was inhibited by losartan in a dose-dependent manner.CONCLUSION:AngRem104 is a novel nuclear protein related to the expression of fibronectin and could be up-regulated by AngⅡ in human MC.     

Protective role of losartan in reversion of hypertensive calcium overload and glomerular injury

AIM:To investigate the relation between cytosolic calcium and glomerular injury in hypertension.METHODS:The normotensive control (WKY) and spontaneously hypertensive rat group(SHR) with or without treatment (losartan 20 mg·kg^-1·d^-1) were compared. Intralymphocytic free calcium level and ultrastructural changes in glomerulus were observed at three and eight months, respectively.RESULTS: The results demonstrated early impairment in glomerulus and elevation of cytosolic calcium at three months in SHR group, at eight months, aggravation of impairment in glomerulus correlating with calcium elevation was shown. Losartan significantly attenuated the above pathologic changes. CONCLUSION:Calcium-overload state was not only related to blood pressure and vessel impairment, but also associated with glomerular injury, which could be reversed by losartan.     

Experimental study on treating rat focal segmental glomerulosclerosis with Decoction of Bu-Shen-Huo-Xue-Xie-Zhuo

AIM:To observe the effects of Decoction of Bu-Shen-Huo-Xue-Xie-Zhuo (BSHXXZ) on focal segmental glomerulosclerosis (FSGS) in rats. METHODS:Unilateral nephrectomy was adopted firstly, one week later adrimycin was intravenously adminstered to 20 rats twice in a 23-day period to establish an advanced focal segmental glomerulosclerosis model in the rat. Changes in urine protein, blood chemistry, and histology of the kidney were investigated for 110 days after unilateral nephrectomy. RESULTS:The BSHXXZ decoction reduced edema, proteinuria, hyperlipidemia, azotemia and ascites, and increased albumin in blood. Light microscopic, electron microscopic, immunohistochemical and polarizing microscopic examination all showed that the pathologic changes in the treatment group were less than that of the model group. CONCLUSION:Decoction of BSHXXZ could markedly improve renal function and delay the progression of glomerulosclerosis and renal interstitial fibrosis.     

Abnormal expression of angiopoietins in glomerulus following podocyte injury and its role in the development of progressive glomerulosclerosis in rats

AIM: To study the potential pathological role of abnormal expression of endogenous angiopoietins in progressive glomerulosclerosis. METHODS: 80 male Wistar rats were randomly allocated into sham operation group (sham, n=25), unilateral nephrectomy group (UNx, n=25) and UNx＋daunorubicin (DRB)group (n=30). The rats in DRB group were intravenously injected with DRB (5 mg/kg) on the seventh and the fourteenth day respectively after excising one kidney. Then, at week 1, 2, 4, 6 and 8, 5, male Wistar rats from each group were taken randomly for determining 24 h urinary protein quantitative measurement (24hUPQ), BUN, Scr, and the kidneys were examined by electronic microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: There was a trend towards an increase respectively in levels of 24hUPQ, Bun, Scr, GSI in DRB from week 2 to week 8. Electronic microscope revealed that podocyte injury presented in DRB group. Expression of Ang1 mRNA and protein in glomerulus in DRB group decreased, while expression of Ang2 protein in glomeruli in DRB group increased. In DRB group, expression of Ang1 protein had a negative correlation with 24hUPQ, BUN, Scr, GSI, expression of Ang2 protein and CoIV protein. Expression of Ang2 protein had a positive correlation with 24hUPQ, BUN, Scr, GSI,expression of CoIV protein. CONCLUSION: Podocyte injury may lead to glomeruli abnormally express angiopoietins. A decrease in expression of Ang1, and upregulation in expression of Ang2 may facilitate progressive glomerulosclerosis in the rat.