Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading

Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. This was accomplished by introducing a human SOST transgene driven by the 8 kb fragment of the DMP1 promoter that also provided osteocyte specificity of the transgene. Right ulnae were subjected to in vivo cyclic axial loading at equivalent strains for 1 min/day at 2 Hz; left ulnae served as internal controls. Endogenous murine Sost mRNA expression measured 24 h after 1 loading bout was decreased by about 50% in TG and wild type (WT) littermates. In contrast, human SOST, only expressed in TG mice, remained high after loading. Mice were loaded on 3 consecutive days and bone formation was quantified 16 days after initiation of loading. Periosteal bone formation in control ulnae was similar in WT and TG mice. Loading induced the expected strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed.     

Temporal expression patterns of BMP receptors and collagen II (B) during periosteal chondrogenesis.

Articular cartilage has a limited ability to repair itself. Periosteal grafts have chondrogenic potential and are used clinically to repair defects in articular cartilage. An organ culture model system for in vitro rabbit periosteal chondrogenesis has been established to study the molecular events of periosteal chondrogenesis in vitro. In this model, bone morphogenetic protein-2 (BMP2) mRNA expression was found to be upregulated in the first 12 h. BMPs usually transduce their signals through a receptor complex that includes type II and either type IA or type IB BMP receptors. Receptors IA and IB play distinct roles during limb development. We have examined the temporal expression patterns for the mRNAs of these receptors using our experimental model. The mRNA expression patterns of these three BMP receptors differed from one another in periosteal explants during chondrogenesis. When these explants were cultured under chondrogenic conditions (agarose suspension with TGF-beta1 added to the media for the first 2 days), the expression of BMPRII mRNA and that of BMPRIA mRNA varied only slightly and persisted over a long time. In contrast, the expression of BMPRIB mRNAwas upregulated within 12 h, peaked at day 5, and fell to a level that was barely detected beyond day 21. Moreover, the expression of BMPRIB mRNA preceded that of collagen type IIB mRNAs, a marker for matrix-depositing chondrocytes. These data support a role for coordinate expression of BMP2 and its receptors early during periosteal chondrogenesis.     

胰高血糖素样肽-1类似物对人成骨细胞Wnt信号通路相关基因表达的影响

目的 观察胰高血糖素样肽-1类似物（利拉鲁肽）对人成骨细胞增殖及Wnt信号通路相关因子mRNA的表达,探讨胰高血糖素样肽-1(GLP-1)与骨代谢的关系。方法 向体外培养的人成骨细胞中分别加入浓度为0mol/L、10-7mol/L、10-8mol/L、10-9mol/L的GLP-1类似物,24h后采用Cell Counting Kit-8(CCK-8)比色法检测成骨细胞增殖率,实时荧光定量PCR（Real-time RT-PCR）法检测Wnt-3a、LRP-5、β-catenin mRNA 的表达。结果 （1）GLP-1促进人成骨细胞增殖（P<0.05）,随着给药浓度的增高,成骨细胞增殖率下降（P<0.05）;（2）低浓度GLP-1（10-9mol/L）上调人成骨细胞中Wnt-3a、LRP-5、β-catenin mRNA 的表达(P<0.05);高浓度GLP-1（10-7mol/L、10-8mol/L）下调人成骨细胞中Wnt-3a、LRP-5、β-catenin mRNA 的表达(P<0.05)。结论 GLP-1促进人成骨细胞的增殖,低浓度时Wnt信号通路可能参与了该调控过程,高浓度抑制Wnt信号通路相关基因的表达。     

Quantitative polymorphism of complement receptor type 1 (CR1) in patients undergoing haemodialysis.

BACKGROUND: The level of complement receptor type 1 (CR1) on erythrocytes (E-CR1) is determined by the presence of high (H) or low (L) expression alleles. We investigated whether acquired loss of E-CR1 occurs in haemodialysis patients and, if so, which factors may contribute to acquired loss of E-CR1 in these patients. METHODS: The E-CR1 level was determined in 195 Japanese haemodialysis patients, and we selected patients with a high or low E-CR1 level. In patients with low E-CR1 expression, sequence analysis of polymorphic sites (A3650G and C5507G) in the CR1 gene was performed. To assess the effect of the type of dialysis membrane used in the patients with low E-CR1 expression, the dialysis membrane was changed from a cellulose membrane to a biocompatible membrane (to a polyacrylonitrile membrane and then to a polysulfone membrane). To evaluate the susceptibility of E-CR1 to proteolysis, erythrocytes were incubated with various concentrations of trypsin, and the level of remaining CR1 on the erythrocytes was determined. RESULTS: Among patients with high E-CR1 expression (n = 30), 87% had HH alleles and 13% had HL alleles. Among patients with low E-CR1 expression (n = 29), 24% had LL alleles, 45% had HL alleles and 31% had HH alleles. Nucleotides 3650G and 5507G in the CR1 gene were associated with the L allele. Nucleotides 3650A and 5507C were associated with the H allele. Only one patient with HH alleles had nucleotides 3650G and 5507C. Three months after changing the haemodialysis membrane, the E-CR1 level significantly increased (P<0.02). The proteolysis curves of E-CR1 of patients with low or high E-CR1 expression and normal controls were similar. CONCLUSION: Use of a non-biocompatible dialysis membrane may contribute to acquired loss of E-CR1 in haemodialysis patients.     

Involvement of the insulin-like growth factor I receptor and its downstream antiapoptotic signaling pathway is revealed by dysregulated microRNAs in bladder carcinoma

ObjectiveUrothelial carcinoma is one of the most common pathological types of bladder cancer. Several studies have shown that dysregulated microRNAs (miRNAs) play an important role in bladder cancer progression. We performed the present miRNA microarray analysis in samples of urothelial carcinoma of the bladder and adjacent normal bladder tissue from Taiwanese patients to investigate dysregulated miRNAs.Materials and methodsTo detect dysregulated miRNAs in urothelial carcinoma of the bladder, samples of tumor and adjacent normal tissues were collected from 10 patients. Tissue samples from three patients were subjected to miRNA microarray analysis, and the remaining tissue samples from the other seven patients were used to validate the results obtained from the microarray data. Potential targets of these dysregulated miRNAs were identified using online databases, including MicroCosm and TargetScan.ResultsA panel of 30 differentially expressed miRNAs with at least fourfold differences in expression compared with normal controls, including 19 upregulated and 11 downregulated miRNAs, was generated. The expression levels of miR-30a-5p, miR-30a-3p, miR-99a, miR-130b, miR-133b, miR-135b, miR-145, miR-195, miR-204, and miR-214 were experimentally verified using real-time RT-PCR analysis. Using an online miRNA target database, we discovered that these dysregulated miRNAs potentially control components of the insulin-like growth factor 1 receptor (IGF1R) signaling pathway.ConclusionOur results indicate that dysregulated miRNAs may be involved in bladder cancer pathogenesis and are potential biomarkers.     

Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin

BACKGROUNDAntagonists of cannabinoid type 1 receptor (CB1) have been shown to promote body weight loss and improve insulin sensitivity. Cannabinoids decrease adiponectin, and CB1 blocker increase adiponectin. However, the mediators of CB1 actions are not well defined. AIMTo investigate whether the beneficial effects of CB1 inhibition are, at least in part, mediated by adiponectin. METHODSWe compared metabolic and inflammatory phenotypes of wild-type (WT) mice, CB1-null (CB1^-/-) and CB1/adiponectin double-knockout (DKO) mice. We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test, and inflammation using flow cytometry analysis of macrophages. RESULTS CB1 ^-/- mice exhibited significantly reduced body weight and fat mass when compared to WT mice. While no significance was found in total daily food intake and locomotor activity, CB1^-/- mice showed increased energy expenditure, enhanced thermogenesis in brown adipose tissue (BAT), and improved insulin sensitivity compared to WT mice. DKO showed no difference in body weight, adiposity, nor insulin sensitivity; only showed a modestly elevated thermogenesis in BAT compared to CB1^-/- mice. The metabolic phenotype of DKO is largely similar to CB1^-/- mice, suggesting that adiponectin is not a key mediator of the metabolic effects of CB1. Interestingly, CB1^-/- mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice; in contrast, DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^-/- mice, suggesting that adiponectin is an important mediator of the inflammatory effect of CB1. CONCLUSIONOur findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms: CB1 regulates energy metabolism in an adiponectin-independent manner, and inflammation in an adiponectin-dependent manner. The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.     

内皮素受体阻断剂对糖尿病大鼠肾脏血管紧张素Ⅱ1型受体表达的影响

目的：观察糖尿病大鼠肾脏血管紧张素Ⅱ1型（AT1）受体的改变以及内皮素受体阻断剂bosentan对其影响。方法：将SD大鼠建成链脲佐菌素诱导的糖尿病模型,设非治疗组、bosentan治疗组和正常对照组。4周后采用免疫组织化学、Western blot及RT－PCR方法检测肾脏AT1受体基因和蛋白表达。结果：与SD对照组相比,糖尿病大鼠存在明显的蛋白尿和内生肌酐清除率升高,其肾脏AngⅡ水平明显升高,同时伴有AT1受体的mRNA和蛋白表达显著下降。bosentan能显著缓解上述异常。结论：糖尿病大鼠肾脏AngⅡ及AT1受体表达明显异常,bosentan具有治疗作用。     

Anosmin-1蛋白通过成纤维生长因子1型受体激活ERK1/2信号通路增强嗅鞘细胞的迁移

目的探究Anosmin-1蛋白对嗅鞘细胞迁移的影响及对成纤维生长因子(FGF)1型受体和ERK1/2信号通路的影响。方法选择SPF级成年雌性SD大鼠40只,7～10周龄,体重250～300 g。提取大鼠嗅球的嗅鞘细胞并纯化,纯化后细胞培养7 d后,采用随机数字表法将所有细胞平均分为四组:对照组(C组),FGF 1型受体激动剂(FGF2)组(F组),Anosmin-1蛋白组(A组)和Anosmin-1蛋白+FGF 1型受体抑制剂(Su5402)组(S组)。C组为空白对照组,培养液中不加任何药物处理;F组为阳性对照组,于培养液中加入FGF2 25 ng/ml; A组于培养液中加入Anosmin-1蛋白2 nmol/L;S组于培养液中加入Anosmin-1蛋白2 nmol/L和Su5402 30μmol/L。四组细胞处理24 h后,采用Transwell法检测嗅鞘细胞迁移能力,Western blot法检测嗅鞘细胞磷酸化ERK1/2(p-ERK1/2)蛋白、磷酸化AKT(p-AKT)蛋白和神经型钙粘连蛋白(N-cadherin)含量,免疫荧光染色法检测N-cadherin荧光强度。结果纯化后的嗅鞘细胞占总细胞的85.6%。与C组比较,F组和A组迁移至下室的嗅鞘细胞明显增多(P0.05),p-ERK1/2蛋白、N-cadherin含量明显升高(P0.05)。与A组比较,S组迁移至下室的嗅鞘细胞明显减少(P0.05),p-ERK1/2蛋白、N-cadherin含量明显降低(P0.05)。S组和C组间、F组和A组间迁移至下室的嗅鞘细胞数量、p-ERK1/2蛋白、N-cadherin含量差异无统计学意义。四组p-AKT蛋白含量差异无统计学意义。结论 Anosmin-1蛋白通过FGF 1型受体激活ERK1/2信号通路,从而上调N-cadherin,增强嗅鞘细胞的迁移能力。     

Association of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression with survival among patients with invasive bladder carcinoma

What’s known on the subject? and What does the study add? SXR and MDR1 are known as responsible for chemo and radiotherapy resistance in some cancers, like kidney cancer (MDR1). Invasive bladder cancer is an aggressive disease, with different behaviour upon its tumoral stage, and also within the same tumoral stage, therefore molecular markers are sought. This study shows a new molecular marker, which has shown as a predictor for bad prognosis cancers, therefore, allowing us for a better patient selection for aggressive therapies.

OBJECTIVE

? To investigate the prognostic value of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression in relation to survival among patients with invasive bladder cancer.

PATIENTS AND METHODS

? The prospective study included 67 patients diagnosed with invasive bladder cancer and treated with radical cystectomy at one of two institutions. ? SXR and MDR1 gene expression was assessed by real‐time quantitative polymerase chain reaction (RT‐PCR) in tumoral and normal tissue from frozen surgical specimens.

RESULTS

? Patients were followed for a mean of 29 months; 31 patients (46%) had progression. ? In univariate analysis, significant predictors of overall survival (OS) were pathological stage, lymph node (LN) status, histological grade, vascular‐lymphatic invasion, and SXR expression. ? In multivariate analysis, independent predictors of OS were LN status (odds ratio [OR], 2.96; P= 0.034), vascular‐lymphatic invasion (OR, 2.50; P= 0.029), and SXR expression (OR, 1.05, P= 0.03). ? Among the 51 patients with negative LNs (pN0), univariate predictors of OS were SXR expression, MDR1 expression, and pathological stage. In multivariate analysis, SXR expression (OR, 1.06; P= 0.01) and MDR1 expression (OR, 3.27; P= 0.03) were independently associated with survival. ? Within the pN0 group, patients with SXR expression had shorter progression‐free survival than did those without expression (P= 0.004). This association persisted in the N0 subgroup with stage pT3–pT4 disease (P= 0.028). However, in the pN1 group SXR expression did not have any influence.

CONCLUSIONS

? For patients with invasive bladder cancer, SXR expression has value as a predictor of survival independent of the standard pathological predictors. ? Its maximum importance appears to be in patients with stage pT3–pT4 pN0 disease.     

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases

BackgroundBone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.MethodsIn total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.ResultsMedian 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73–158.00) vs. 4.00 (range, 2.18–34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73–158.00) and 3.91 µg/L (2.04–34.51) for 1CTP and 48.60 (9.12–1,074.37) and 33.90 (8.72–149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.ConclusionsThe present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.     

Activation of c‐Jun NH2‐terminal kinase 1 increases cellular responsiveness to BMP‐2 and decreases binding of inhibitory Smad6 to the type 1 BMP receptor

Bone morphogenetic protein 2 (BMP‐2) plays a critical role in the differentiation of precursor cells and has been approved for clinical application to induce new bone formation. To date, unexpectedly high doses of recombinant BMP‐2 have been required to induce bone healing in humans. Thus, enhancing cellular responsiveness to BMP‐2 potentially has critically important clinical implications. BMP responsiveness may be modulated in part by cross‐talk with other signaling pathways, including mitogen‐activated protein kinases (MAPKs). c‐Jun NH₂‐terminal kinase (JNK) is a MAPK that has been reported to be required for late‐stage differentiation of preosteoblasts and BMP‐2‐induced differentiation of preosteoblasts and pleuripotent cells. In this study we determined that MC3T3‐E1‐clone 24 cells (MC‐24) can be induced by BMP‐2 to differentiate into mineralizing osteoblast cultures. Using this inducible system, we employed both JNK loss‐of‐function and gain‐of‐function reagents to make three key observations: (1) JNK is required for phosphorylation of Smad1 by BMP‐2 and subsequent activation of Smad1 signaling and osteoblast differentiation, (2) JNK1, but not JNK2, is required for BMP‐2‐induced formation of mineralized nodules, and (3) JNK1 activation decreases binding of inhibitory Smad6 to the type I BMP receptor (BMPR‐I) and reciprocally increases binding of Smad1, both observations that would increase responsiveness to BMP‐2. Understanding this and other pathways that lead to increased cellular responsiveness to BMPs could greatly aid more cost‐effective and safe clinical delivery of these important molecules. © 2011 American Society for Bone and Mineral Research.     

胆固醇结石病人肝脏SRBI及其转录调节因子LRH-1基因表达的研究

目的:研究胆固醇结石病人BI型清除剂受体(scavengerreceptorBtypeI,SRBI)及其转录调节因子肝脏受体类似物1(liverreceptorhomologue1,LRH-1)的表达,以探讨胆固醇结石发病的机制。方法:对20例胆囊胆固醇结石病人和10例无胆石症对照者测定血清脂质、胆汁成分和计算胆汁胆固醇饱和指数。以实时定量PCR法测定肝脏SRBI和LRH-1mRNA的表达量。结果:胆石组胆石平均胆固醇含量(86.68±5.26)%,均为胆固醇结石。胆石组病人血清高密度脂蛋白(HDL)显著低于对照组[(0.86±0.62)mmol/L比(1.42±0.56)mmol/L,P<0.01]。胆石组胆汁胆固醇在总脂中的摩尔百分比和胆固醇饱和指数显著高于对照组[(7.80±2.06)mol%比(5.26±2.80)mol%,P<0.05]。胆石组SRBI基因mRNA表达量与对照组比较显著增高(2.48±0.44比1.00±0.23,P<0.05),胆石组LRH-1表达也高于对照组(2.05±0.29比1.00±0.28,P<0.05)。结论:胆固醇结石病的主要病理生理异常为胆汁胆固醇过饱和。肝脏LRH-1、SRBI表达增高,参与了胆固醇过饱和胆汁形成,并促进了胆固醇结石形成。     

Effects of the angiotensin II type 1 receptor antagonist candesartan,compared with angiotensin-converting enzyme inhibitors,on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy

Background. We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen. Methods. Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 ± 3 months. The urinary excretion of albumin and urinary type IV collagen was measured. Results. Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group. Conclusion. It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.     

Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetes and nephropathy.

BACKGROUND: A growing body of evidence supports the concept that treatment with the newer angiotensin type-1 receptor blockers (ARBs) improves glucose homeostasis under conditions wherein it is impaired. Controversy exists, however, regarding the ability of losartan, an older ARB, to exert comparable improvement. The present study was undertaken to evaluate the effects of losartan on glucose homeostasis in subjects with type 2 diabetes and nephropathy. METHODS: Twenty-seven subjects with type 2 diabetic nephropathy were enrolled in this prospective, randomized, controlled study. Losartan (100 mg daily) or the calcium channel blocker amlodipine (10 mg daily) was administered for a period of 3 months. Fasting blood glucose, serum insulin and C-peptide concentrations were measured at baseline and at the end of the study. Oral glucose tolerance tests were performed to evaluate insulin sensitivity and beta-cell responsiveness. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Fasting blood glucose, HbA1c, AUC glucose, and urinary protein values were significantly decreased in the losartan group as compared with the amlodipine group (P<0.05). Furthermore, C-peptide concentrations, the insulin sensitivity index, and the insulin-to-glucose ratio were significantly increased after 3 months of therapy with losartan as compared to amlodipine (P<0.05). Reductions of fasting insulin concentrations and HOMA-IR were also observed for the losartan group; however, reductions were not significant when compared with the amlodipine group. CONCLUSION: In addition to reducing urinary protein excretion, losartan at 100 mg daily increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetic nephropathy.     

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage

OBJECTIVE: To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. METHODS: Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. RESULTS: Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. CONCLUSIONS: Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.     

NK1受体在大鼠牙髓及牙周组织中的表达及意义

目的:观察NK1受体在大鼠牙髓及牙周组织中的表达情况。方法:采用冰冻切片和ABC免疫组化方法,检测NK1受体在大鼠牙髓及牙周组织中的表达。结果:NK1受体在大鼠牙周及牙髓组织内分布广泛,在牙周膜成纤维细胞、成牙骨质细胞、成牙本质细胞均呈强阳性表达;在牙髓成纤维细胞和牙槽骨细胞呈弱阳性表达;在牙齿根髓和冠髓内可发现染色阳性的血管样条索。结论:P物质可能直接作用于牙髓和牙周组织,细胞在牙髓及牙周炎症、修复反应中发挥作用。     

黑皮素-1受体在增生性瘢痕组织中的表达与分布

目的:研究黑皮素-1受体(mel anocort in-1 recept or,MC-1R)在增生性瘢痕组织中的表达和分布特点,探讨它与增生性瘢痕形成的关系。方法:利用兔抗人MC-1R抗体进行免疫组织化学染色,并测定8例增生性瘢痕,8例表浅性瘢痕和16例同体的正常皮肤标本切片染色后的平均灰度值,分别检测MC-1R在上述不同组织中表达的差异。结果:在正常皮肤、表浅瘢痕和增生性瘢痕中,MC-1R免疫阳性产物呈棕黄色颗粒状,主要分布于表皮基底层细胞胞浆中。在增生性瘢痕组织中,MC-1R灰度值(159.2±5.5)明显高于正常皮肤(134.7±5.9)和表浅性瘢痕(135.9±9.3),差异显著(P<0.01)。而后两者无明显差异(P>0.05)。结论:增生性瘢痕的形成可能与MC-1R在增生性瘢痕组织中表达明显减少,由其介导的α-黑色素细胞刺激素(α-melanocyte stimul ating hormone,α-MSH)对胶原蛋白的代谢和细胞外基质沉积的调节作用减弱有关。