Expression and modulation of connective tissue growth factor in renal interstitial fibrosis

CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstream effector of TGF-β acting on interstitial cells to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis.     

Effects of uremic serum of different molecular weight groups ongene and protein expression of connective tissue growth factor gene and proteinexpression in human renal tubular epithelial cells

AIM:To investigate the effects of uremic serum of different molecular weight groups on gene and protein expression of connective tissue growth factor (CTGF) in human renal tubular epithelial cells.METHODS:The serum from 40 chronic renal failure patients and 20 healthy volunteers were collected and uremic serum was segregated to three groups: >10 000 D,5 000-10 000 D,<5 000 D by 10 000 D and 5 000 D molecular weight Centricon Plus 20 Centrifugal Filter Devices.The protein expression of CTGF was examined by Western blotting.The mRNA expression of CTGF was detected by RT-PCR.RESULTS:CTGF gene expression were increased in 2.5%-20% uremic serum groups compared with that in normal control group,and it was the highest in 10% uremic serum groups.CTGF gene expression was increased significantly in molecular weight >10 000 D and 5 000-10 000 D groups,and the highest was in >10 000 D group,but it was no significant difference in <5 000 D group compared with that in normal control group.CTGF protein was increased in different molecular weight uremic serum groups compared with that in normal control group,and gradually increased following the increasing of uremic serum concentration and it was the highest in molecular weight >10 000 D group.CONCLUSION:Human renal tubulointerstitial fibrosis was accelerated significantly by uremic toxin,especially molecular weight >10 000 D uremic toxin through promoting the gene and protein expression of CTGF in renal tubular epithelial cells in patients with chronic renal failure.     

Impact of hydrogen sulfide donor on endothelin-1 and connective tissue growth factor expression in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To explore the possible impact of hydrogen sulfide (H2S) donor-sodium hydrosulfide (NaHS) on endothelin-1 (ET-1) and connective tissue growth factor (CTGF) expressions in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty-two male SD rats were randomly divided into 4 groups: shunt group, shunt+NaHS group, sham group and sham+NaHS group. Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 11 weeks of experiment, rat systolic pulmonary artery pressure (SPAP), lung tissue H2S, plasma ET-1 concentration and lung tissue ET-1mRNA expression, as well as pulmonary artery CTGF protein expression were detected.RESULTS: After 11 weeks of experiment, SPAP, lung tissue ET-1mRNA, plasma ET-1 as well as pulmonary artery CTGF expressions were increased markedly, respectively, whereas H2S in lung tissue decreased significantly in rats of shunt group as compared with that in sham group (all P<0.05). After administration of NaHS for 11 weeks, H2S in lung tissue increased significantly, whereas SPAP, plasma ET-1 and lung tissue ET-1 mRNA expression as well as pulmonary artery CTGF protein expression decreased significantly, respectively, in rats of shunt+NaHS group as compared with that in shunt group (all P<0.05).CONCLUSION: NaHS might be involved in the development of pulmonary hypertension induced by high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expressions in lung tissues of rats.     

马协不育花药药隔ATPase超微结构定位

马协可育花药单核期和二核期药隔维管束薄壁细胞核、 筛分子质膜、 胞间连丝及其转运物、 药隔薄壁细胞液泡膜、 胞间隙及淀粉粒表面具有ATPase活性。 马协不育花药单核期维管束薄壁细胞核变形, 核内有弥散的异染色质, 随后异染色质团转移到核边缘, 并表现出减少的趋势; ATPase主要定位于核异染色质、 线粒体、 液泡、 质     

Effect of Ginkgo biloba extract on the expression of connective tissue growth factor in the initiating stage of fibrosis in lungs of rats

AIM: To study the effect of Ginkgo biloba extract (GbE) on the expression of connective tissue growth factor (CTGF) in the initiating stage of pulmonary fibrosis of rats after administration of bleomycin (BLM).METHODS: The expression of CTGF in lungs was detected by Western blotting. The content of hydroxyproline was assayed by the method of chloramines T. The content of malondialdehyde (MDA) in plasma was investigated by colorimetry.RESULTS: On day 14 after administration of BLM, the contents of CTGF in lungs and MDA in plasma in BLM+NS group were higher than those in NS group, respectively (P<0.05; P<0.01). On day 30 after BLM, the contents of hydroxyproline in lungs and MDA in plasma in BLM+NS group were higher than those in NS group, respectively (both P<0.01). Treatment with GbE ameliorated the above changes induced by BLM. CONCLUSION: GbE ameliorates the up-regulation of CTGF in the initial stage of fibrosis in lungs of rats after administration of BLM. GbE prevents the hyperoxidative injury in lungs of rats after BLM, which might be one of mechanisms underling the effect of GbE on CTGF.     

Expression of low density lipoprotein receptor-related protein in renal interstitial fibrosis

AIM: To understand the expression of low density lipoprotein receptor-related protein (LRP) in tubulointerstitial fibrosis of unilateral ureter obstruction (UUO) rats. METHODS: The localization of LRP within kidneys were assessed by immunohistochemical staining, the protein level of LRP and connective tissue growth factor (CTGF) in kidney were analysised by Western blot. RESULTS: The location of LRP positive-staining and the protein level of LRP were in the same tendency with CTGF, the level of LRP had strong correlationship with the level of CTGF (r=0.786, P＜0.01); The expression of LRP was positive correlated with tubular-interstitial injury index (r=0.800, P＜0.01). Enalapril treatment downregulated LRP level at 9 days time point. CONCLUSION: The expression of LRP was increased according to the progression of interstitial fibrosis in UUO rats, implicating that LRP may act as receptor of CTGF to mediate the profibrotic effect of CTGF.     

Expression of CTGF and its role in the streptozotocin-induced diabetic rat kidney

AIM:To investigate the change of connective tissue growth factor(CTGF) expression and its role in streptozotocin-induced diabetic rat kidney. METHODS:Male SD rats were randomly divided into two groups: control(sham operated rats, group C，n=32) and diabetic rats (group DN，n=35). Rats in each group were sacrificed at 1, 2, 4, and 8 weeks respectively after induction of diabetes. Body weight（BW）, blood glucose（BG）, 24-hour urine volumn（UV）, kidney weight, KW/BW,24-hour urinary albumin excretion (24Ualb), creatinine clearance (Ccr), kidney weight (KW), KW/BW, glomerular area (A_G), proximal tubular area (A_T) and the width of GBM、TBM at each time point were measured. Expression of CTGF and α-SMA were detected by immunostaining. RESULTS:There was a significant increase of 24 h Ualb, Ccr, KW/BW, A_G, V_G and the expression of CTGF in glomeruli and tubuli from week 1 onward in diabetic rats compared with those in group C (P<0.05, P<0.01, respectively), and an increasing expression of α-SMA mainly located in dilated tubuli from week 4 was found in group DN, which was more evident at week 8 accompanied by the decrease in A_T. Diabetic rats also had a significant increase in A_T from week 1 onward, which peaked at week 4. CONCLUSION:In the early stage of DN, the time-dependently upregulated CTGF might mediate the renal hypertrophy, which might be associated with the subsequent tubular epithelial-mesenchymal transdifferentiation (EMT) and renal fibrosis.     

双峰驼肝的形态结构研究

用光镜与电镜研究了我国３５例双峰驼肝的解剖与组织结构。肝略呈三角形，体大，重达８～１２ｋｇ，其外观和马肝相似，都分为左叶、右叶和中叶（包括方叶和尾叶），但脏面有不少沟裂。组织上肝也由肝小叶组成。肝细胞浆中常有胆红素颗粒。肝被膜厚似脾并向内伸入。小叶周围区的结缔组织不多，但在门管区的小叶间动脉、静脉和胆管外周，结缔组织则形成厚鞘。小叶下静脉壁也有大量胶原纤维束。小叶内肝实质的支持组织包括狄氏间隙的网状纤维和中央静脉近周的胶原纤维束。电镜发现，窦状隙内皮细胞衬里层较厚，细胞浆中线粒体很少，而吞饮泡和微丝、微管却相当多。狄氏间隙明显。肝细胞含大量细胞器和内含物。作者还发现肝细胞群中有滑面内质网较多的“明细胞”，推测这种细胞同白蛋白的合成有关。