Possible roles of basic fibroblast growth factor in the pathogenesis of moyamoya disease: an immunohistochemical study

Prominent features of moyamoya disease are fibrocellular thickening of the intima and enhanced angiogenesis. The pathogenesis of moyamoya disease is, however, unknown. Basic fibroblast growth factor (FGF) is an angiogenic factor as well as a potent mitogen for a number of cell types including vascular endothelial and smooth-muscle cells. In order to test the possibility that basic FGF takes part in the pathogenesis of moyamoya disease, the authors tested for the presence of this factor using a mouse monoclonal antibody against human recombinant basic FGF. The surgical specimens studied included two sections of the superficial temporal artery (STA) and four samples of dura mater from four patients with moyamoya disease. Surgical specimens were obtained from three patients with other diseases as control tissue. Sections of the STA obtained from the patients with moyamoya disease showed strong basic FGF immunoreactivity in endothelial and smooth-muscle cells, while control sections had only faint and scattered immunoreactivity. All sections of the dura mater obtained from the patients with moyamoya disease also revealed more intense immunohistochemical staining of basic FGF in meningeal and vascular cells than did control sections. These observations indicate that the amount of basic FGF is increased in the tissues of patients with moyamoya disease; thus, basic FGF may play an important role in the pathogenesis of moyamoya disease.     

bFGF对促进大鼠移植缺血皮瓣血管化的实验研究

目的 探讨碱性成纤维细胞生长因子(bFGF)对大鼠移植皮瓣成活作用的影响.方法 Wistar大鼠48只,按月龄随机分为A、B、C、D四组,每组12只.制作移植皮瓣模型.A、C组的大鼠多次多点每点注射bFGF 60 U(0.015 ml);B、D组给予等量生理盐水作为对照.分别于5 d、14 d观察皮瓣的存活率,分别取相同部位皮瓣组织块行病理组织学检查,并采用计算机图像分析系统和免疫组化方法计算血管密度和血管内皮生长因子(VEGF)阳性血管数.结果 大鼠缺血皮瓣血管密度及VEGF阳性表达的血管数A组[(分别为(134.21±4.86)个/mm~2,(14.63±2.25)条]多于B组[分别为(118.48±2.31)个/mm~2,(7.45±1.43)条],C组[分别为(128.67±4.58)个/mm~2,(11.39±1.61)条]多于D组[分别为(115.32±2.18)个/mm~2,(6.96±1.35)条],差异均有统计学意义(P<0.05);A组和C组比较,差异无统计学意义(P>0.05).结论 在不同月龄大鼠移植皮瓣内注射bFGF蛋白可促进皮瓣血管新生,改善移植皮瓣缺血状态,提高皮瓣成活率.     

Ischemia increases the angiogenic potency of basic fibroblast growth factor (FGF-2)

The aim of this study was to investigate the angiogenic response to exogenously administered basic fibroblast growth factor (FGF-2) in normal and ischemic skin, using the hairless mouse ear microcirculatory model. The hairless mouse ear is a well-established model for in vivo studies of skin microcirculation. Using this model, angiogenesis- and angiogenesis-associated changes in the microcirculation can be directly and continuously viewed and quantified in a variety of different experimental settings. To create ischemia in the mouse ear, all but one of the three to four feeding vessels nourishing the ear were ligated 3 days prior to a local subdermal injection of FGF-2 (9.3 + 1–0.5 mm/mm²) or saline into the dorsum of the ears. Angiogenesis was quantified by direct observation, at high magnification, of the injection site where increases in total vessel length (TVL) were measured repeatedly over 18 days following injection. We found a significant (P < 0.01) increase in TVL in normal and ischemic ears injected with FGF-2. Saline injection also induced a significant increase in TVL in ischemic ears. However, the angiogenic response to FGF-2 in ischemic ears was significantly stronger than saline alone in ischemic ears or saline or FGF-2 in normal ears. This response could be used clinically to accelerate angiogenesis and thus increase perfusion in ischemic tissue. © 1997 Wiley-Liss, Inc. MICROSURGERY 17:452–456 1996     

Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.

Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. Female Sprague-Dawley rats (n = 55) sustained a 10-g weight-drop injury to the lower thoracic spinal cord (T10) from a height of 12.5 mm using the NYU impactor. A micro-infusion system (Alzet minipump) was used to continuously deliver drugs or vehicle directly into the epicenter of the contused spinal cord starting 1 or three h postinjury. At the end of 7 days, animals were perfused and the cords removed for histopathological analysis. Longitudinal serial sections were cut on a freezing microtome and stained with cresyl violet. Areas of central necrosis, partial preservation, and total zone of tissue injury were identified and traced by an independent reviewer using a computer based imaging system. The mean total zone of injury in five animals receiving vehicle infusion was 18.04+/-4.20 mm3. The mean zone of partial preservation in these animals was 16.46+/-3.32 mm. Basic fibroblast growth factor reduced the total zone of injury by 33% [p<0.01, least significant difference (LSD) of Fisher] in five animals and the zone of partial preservation by 32% (p<0.01, LSD of Fisher) when compared to controls. There were trends toward reduction in total zone of injury and zone of partial preservation in rats treated with IL-4, CNTF, and NGF versus vehicle; however, none of these reached statistical significance. No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.     

Epidermal growth factor and prostatic carcinoma: an immunohistochemical study

Associations between epidermal growth factor (EGF) and carcinoma of the prostate (CAP) have not been systematically investigated. We used indirect immunohistochemical techniques to demonstrate cytoplasmic EGF in paraffin-embedded sections of the following primary prostatic tissues: benign prostatic hyperplasia (BPH) (N = 10), BPH adjacent to CAP (N = 42), clinically localized CAP (N = 45), untreated metastatic CAP (N = 10), and metastatic CAP after varying periods of androgen deprivation (N = 10). In six of the latter 10 cases biopsies of the primary tumor obtained before androgen deprivation therapy were also available for study. Three of the BPH specimens (6%) and 44 of the CAP specimens (68%) stained. Forty per cent of the localized tumors stained but all untreated and treated metastatic tumors stained (p less than 0.01). There were direct but statistically insignificant correlations between the demonstration of EGF and both the Gleason score of localized and untreated metastatic tumors and the pathologic stage of localized tumors. The proportion of malignant cells stained in EGF positive tumors was similar regardless of Gleason score, pathologic stage or the presence or absence of metastases. However, the proportion of cells stained was greater in five of six specimens obtained during hormonal deprivation compared to specimens of the same tumor obtained before treatment. These data suggest that some prostatic cancers interact with EGF and that the interaction may be influenced by the androgenic milieu.     

Characterizing the mitogenic effect of basic fibroblast growth factor in the adult rat striatum

The limited regenerative capacity of the adult central nervous system (CNS) renders it unable to fully recover from injury or disease. Although stem and progenitor cells have been shown to reside throughout the brain, in most regions they exist as quiescent cell populations and do not divide sufficiently to replace damaged or destroyed cells. In an effort to stimulate the proliferative capacity of these multipotent cells, we sought to determine the in vivo response of the adult CNS to an exogenous application of basic fibroblast growth factor (bFGF), a known mitogen to stem and progenitor cells. Specifically, we administered bFGF to the striatum of adult rats at varying concentrations (1, 10, 100, 1,000, or 10,000 ng/mL in saline) so as to establish a dose response curve for bFGF-induced cell proliferation. Forty-eight hours following bFGF administration, animals were injected with 5-bromodeoxyuridine to label dividing cells. Of the doses assessed, we found that 1,000 ng/mL bFGF generated the greatest proliferative response over that observed in animals given a control saline injection. Further, the proliferative response of the striatum to bFGF administration could be enhanced twofold by supplementing this growth factor with heparin sulfate, a factor that facilitates the binding of bFGF to its receptors. By determining the maturational fate of the proliferating cell population, we found that a significant proportion of newly generated cells resulting from bFGF administration differentiated into astrocytes. Collectively, these studies demonstrate the potential of bFGF to promote proliferation in the adult brain, which can be exploited to facilitate cell replacement therapies.     

Microcirculatory changes following reperfusion insult in diabetic rat skeletal muscles

We investigated the microcirculatory changes of ischemia/reperfusion injury in the diabetic rat cremaster muscle as well as the therapeutic effect of insulin. Streptozotocin-induced diabetic rats were maintained hyperglycemic for up to 8 weeks or were treated with insulin in the diabetic period. The rat cremaster muscle was prepared as an island flap and subjected to 2-h clamp ischemia followed by 1-h reperfusion. In nonischemic conditions, effective concentrations for 50% response (EC50) of serial orders of arterioles to norepinephrine were higher in diabetic muscles. Ischemia/reperfusion insult significantly decreased the EC50 of arterioles in the normal group, but not in the diabetic group. Light microscopy showed that the diabetic cremasters had more collapsed capillaries and smooth muscle-disarranged arterioles. Insulin therapy showed significant improvement in the diabetes-caused reduction of perfused capillary density, but not in the contractility of the diabetic arterioles. These results indicate that diabetes mellitus may damage the skeletal muscle microvasculature irreversibly and make it less responsive to autonomic regulation. Insulin therapy can improve capillary perfusion, but not the microvascular reactivity of diabetic muscles.     

Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study

OBJECTIVE: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. METHODS: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 microg/kg (mid-dose, n = 6, 30 injections/animal), 6 microg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 microg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. RESULTS: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 +/- 0.04 at 1 month and 0.75 +/- 0.07 at 3 months compared with 0.68 +/- 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 +/- 0.03 at 1 month and 0.72 +/- 0.04 at 3 months compared with 0.67 +/- 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 +/- 0.06 at 1 month and 0.85 +/- 0.05 at 3 months (P <.001) compared with 0.67 +/- 0.04 at baseline. In the high group, myocardial blood flow was 0.81 +/- 0.06 at 1 month and 0.83 +/-.04 at 3 months (P =.03) compared with 0.71 +/- 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. CONCLUSIONS: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 microg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.     

Hepatocyte growth factor in hepatic allograft biopsies: an immunohistochemical study

Hepatocyte growth factor (HGF) is a multipotent growth factor that is a powerful stimulator of DNA synthesis in a variety of cell types, especially hepatocytes. This factor is produced by nonparenchymal cells in the liver, presumably Kupffer cells, Ito cells, and sinusoidal endothelial cells. Research has shown that HGF is involved in tissue regeneration, wound healing, normal tissue growth, tumor progression, embryogenesis, and tumor invasion. Elevated serum levels of HGF have been documented in patients with acute renal failure and in renal transplant recipients; however, the importance of HGF in liver transplantation is unknown. The aim of this study was to determine whether induction of HGF expression is associated with acute rejection in liver transplants. We assessed the presence and density of HGF in hepatic allograft biopsy specimens compared with those from a control group of healthy patients.     

Effect of basic fibroblast growth factor on insulin secretion from microencapsulated pancreatic islets: an in vitro study

Microencapsulation of pancreatic islets represents a potentially effective method to prevent graft rejection in allotransplantation or xenotransplantation without the need of immunosuppression. Adequate insulin secretion and glucose responsiveness of microencapsulated pancreatic islets has been regarded as a prerequisite for successful transplantation. The microencapsulated pancreatic islets were respectively cultured in bFGF+ RPMI-1640 medium (bFGF+) or bFGF- RPMI-1640 medium (bFGF-) for 21 days. The functional activities of microencapsulated pancreatic islets were assessed by measuring basal insulin secretion and stimulated insulin release at different time points. The results revealed that microencapsulated pancreatic islets in the presence of bFGF demonstrated an increase in basal insulin secretion. Furthermore, microencapsulated pancreatic islets in the presence of bFGF demonstrated a marked stimulated insulin release and relative stability of stimulation indices (SI). The results in the perifusion study showed that microencapsulated pancreatic islets in the presence of bFGF maintained good glucose responsiveness over the course of culture period as well. These results indicate that bFGF has a beneficial effect on insulin secretion from microencapsulated pancreatic islets during in vitro culture. New strategies for preserving and improving function of microencapsulated pancreatic islets prior to transplantation may be developed by application of growth factors or other factors.     

Role of hypoxia in growth factor responses: differential effects of basic fibroblast growth factor and platelet-derived growth factor in an ischemic wound model

Both recombinant basic fibroblast growth factor and platelet-derived growth factor-BB homodimer are potent inducers of new tissue generation in models of normal dermal repair. However, their therapeutic targets include chronic wounds, which are frequently characterized by local tissue hypoxia. To explore the potential of recombinant basic fibroblast growth factor and platelet-derived growth factor-BB homodimer to stimulate more clinically relevant repair, we created an ischemic dermal wound on the rabbit ear by ligating two of the arteries which feed the ear. Both recombinant basic fibroblast growth factor and platelet-derived growth factor-BB homodimer stimulated marked neovascularization of the wound (p < 0.0001), but only recombinant platelet-derived growth factor-BB homodimer accelerated and augmented granulation tissue formation (p = 0.01) and reepithelialization. This study is the first demonstration of a direct angiogenic effect of recombinant platelet-derived growth factor-BB homodimer in vivo. India ink perfusion coupled with endothelial cell-specific histochemistry showed that nearly all the neovessels in all wounds were functional, indicating rapid capillary morphogenesis. In the nonischemic (normal) rabbit ear, recombinant basic fibroblast growth factor and platelet-derived growth factor-BB homodimer accelerated healing comparably, as expected. Higher doses of recombinant basic fibroblast growth factor also failed to elicit stimulatory effects in ischemic wounds. These results indicate that differential responsiveness to growth factors is related to local tissue hypoxia, angiogenesis alone is an insufficient stimulus for repair. These data also suggest new therapeutic approaches for the treatment of chronic wounds.     

碱性成纤维细胞生长因子对兔全脑缺血再灌注损伤的保护作用

目的探讨碱性成纤维细胞生长因子(bFGF)对兔脑缺血再灌注损伤的保护作用。方法 24只大白兔,随机均分为假手术组、对照组和bFGF组,以“四血管阻断 体循环低血压”法制作兔心搏骤停后脑缺血再灌注损伤模型。bFGF组在缺血30min时将bFGF 30μg／kg经耳缘静脉注入,此后以10μg·kg-1·h-1微泵输入持续6 h,对照组仅应用等剂量的生理盐水,假手术组仅分离血管而不作其他处理。持续监测动脉血压、体温、心率,分别于夹闭血管前(T0)、开放血管即刻(T1)、开放血管后 0．5(T2)、1(T3)、3(T4)、6h(T5)测定血清神经元特异性烯醇化酶(NSE)、S-100B蛋白浓度,实验结束取脑组织测定脑水含量,在电镜下观察其超微结构。结果对照组、bFGF组T4 ,5时血清NSE、S-100B浓度高于假手术组(P<0．01);bFGF组T4 ,5时血清NSE、S-100B浓度低于对照组(P<0．05)。血清NSE与S- 100B浓度间的相关系数为0．736(P<0．01)。对照组和bFGF组脑水含量高于假手术组(P<0．01)。 bFGF组脑组织病理改变比对照组轻。结论 bFGF对兔脑缺血再灌注损伤有一定的保护作用。     

The effect of basic fibroblast growth factor on scarring.

Granulation-tissue myofibroblasts are important in wound contraction, disappearing in normal scars but persisting in hypertrophic scars. While transforming growth factor beta 1 (TGF-beta 1) is implicated in excessive scarring and induces the accumulation of myofibroblasts, the role of basic fibroblast growth factor (FGF-2) on scarring remains unreported. Four linear full-thickness incisions, each 20 mm long, were made dorsally on 25 adult male Hooded Lister rats. In each animal, one wound was unmanipulated (control), one was injected with TGF-beta 1 (positive control), one with vehicle alone and one with FGF-2 (test). The wounds were injected daily for 5 days. Animals were sacrificed in groups of five on days 5, 10, 15, 20 and 30 after wounding. Wounds were subjected to tensiometry. Sections were stained for collagen fibres, immunostained for myofibroblasts and studied under light microscopy and electron microscopy. Myofibroblasts were present in the granulation tissue on day 5, reached their maximum number on day 10 and disappeared from all wounds by day 30. Treatment with FGF-2 inhibited this transient phenotypic change of granulation-tissue fibroblasts into myofibroblasts, relative to controls (15.23% versus 58.71%, 15.23% versus 54.71% and 15.23% versus 53.15%; P<0.003 on day 10, paired t-test). Test collagen-fibre orientation resembled that of the normal dermis, in contrast to that of the control wounds. Test wound breaking strength was unreduced. These results suggest a possible anti-scarring effect of FGF-2 during wound healing.     

Increased gene expression of scatter factor—hepatocyte growth factor and basic fibroblast growth factor in granulation tissue in the rat

Scatter factor-hepatocyte growth factor is a protein secreted by fibroblasts which disperses colonies of epithelial cells and keratinocytes in culture. The factor is also a patent mitogen for hepatocytes, synthesized in the liver. Basic fibroblast growth factor, another heparin-binding factor, is most abundant in the brain but also plays a role in wound healing. Using a solution hybridization/RNAase protection assay, we have measured the abundance of messenger RNA for scatter factor-hepatocyte growth factor and basic fibroblast growth factor in granulation tissue obtained from subcutaneously Hunt-Schilling wound cylinders. The levels of scatter factor-hepatocyte growth factor messenger RNA increased after weeks 2 through 4 to a twofold higher level in weeks 5 through 7 after implantation of the cylinders, whereas no changes in basic fibroblast growth factor messenger RNA levels were noticed. At week 3 after implantation of the cylinders, scatter factor-hepatocyte growth factor messenger RNA levels in granulation tissue were more than threefold higher than in skin dermis fibroblasts but markedly lower than in the liver. The abundance of basic fibroblast growth factor messenger RNA was also significantly increased in granulation tissue compared with dermis but, as expected, markedly lower than in the brain. In conclusion, the gene expression of the scatter factor-hepatocyte growth factor, as well as basic fibroblast growth factor, is increased in granulation tissue. Because there was a time-dependent increase in the expression of scatter factor-hepatocyte growth factor, it is hypothesized that scatter factor-hepatocyte growth factor acts as a signal from fully developed granulation tissue to stimulate skin epithelial cells to scatter over the wound.     

Toward surgical angiogenesis using slow-released basic fibroblast growth factor.

OBJECTIVE: Therapeutic angiogenesis using basic fibroblast growth factor (bFGF) in coronary artery disease has been documented in a number of papers. However, the effectiveness is discrepant among documents. In this study, we evaluated the distribution of bFGF in the rat heart by different administration methods, and investigated the efficacy of slow-released administration of bFGF using biodegradable hydrogel microspheres (bFGF microspheres) in a pig infarction model toward an enhanced coronary bypass surgery. METHODS: Heart failure due to myocardial infarction was induced in rats and pigs. In the rat study, free form of bFGF (central venous injection, intracoronary injection, and intramyocardial administration) and bFGF microspheres (intramyocardial administration) were given 4 weeks later. The remaining radioactivity of bFGF in the hearts was estimated 1, 24, and 72 h later. On the other hand, the pigs were randomized into two groups 4 weeks after myocardial infarction. While the control group (n=8) had gelatin hydrogel microspheres with saline, the FGF group (n=8) received bFGF microspheres in the left ventricular (LV) wall. RESULTS: In the rat study, after intramyocardial administration of bFGF microspheres, more bFGF remained in the rat heart 72 h later compared with the other methods (P<0.0001). In the pig study, 4 weeks after the treatment, the FGF group had smaller LV diastolic diameter (48.7+/-5.3 vs. 56.7+/-5.2 mm, P<0.01) than the control group. LV end-systolic elastance was higher in the FGF group (2.96+/-1.2 vs. 1.06+/-0.3 mmHg/ml, P<0.01). In microscopic examinations, many neovessels were found in and around the scar tissue, and the vascular density in the FGF group was significantly higher (61.5+/-18.3 vs. 153.0+/-29.0/mm2, P<0.01). In addition, the infarcted LV walls were less expanded and more thickened in the FGF group. CONCLUSIONS: Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery.     

Interaction of basic fibroblast growth factor with bovine growth plate chondrocytes.

The basic fibroblast growth factor (bFGF) family of peptides influences a wide range of cellular actions. To better understand the possible role of bFGF in the growth plate, we have characterized the interaction of this growth factor with isolated bovine growth plate chondrocytes. Basic FGF interacts with two classes of binding sites on these cells. One is consistent with high-affinity bFGF receptors and the other with low-affinity heparin-like binding sites on the chondrocyte surface. Radiolabeled bFGF binding studies revealed approximately 4 x 10(6) binding sites per cell, with a Kd of approximately 42 nM. Graded concentrations of heparin or NaCl competed with [125I]-labeled bFGF in a dose-dependent fashion, reducing [125I]-labeled bFGF binding by 75 and 97%, respectively. The data suggest the presence of a high-capacity, low-affinity class of binding sites with the properties of a heparin-like moiety. Affinity cross-linking of [125I]-labeled bFGF to chondrocytes labeled two principal species with apparent molecular masses of 135 and 160 kDa. Labeled bFGF was specifically displaced from both species by subnanomolar concentrations of unlabeled bFGF. These high-affinity, low-capacity binding sites are characteristic of classical bFGF receptors. Binding of [125I]-labeled bFGF to these sites was also influenced by heparin, consistent with coregulation of binding to the two classes of binding sites. The data suggest that bFGF participates in the regulation of skeletal growth at the growth plate and that this regulation may involve bFGF interaction with at least two distinct classes of binding sites.     

腹膜透析对碱性成纤维生长因子在大鼠腹膜表达的影响

腹膜超滤衰竭(UFF)是长期腹膜透析(PD)的主要并发症,而UFF患者腹膜组织病理检查显示新生血管明显增多.碱性成纤维生长因子(bFGF)是目前公认的促血管生成因子,在腹膜间皮细胞呈结构件表达.在CAPD患者腹透液中也可榆测到bFGF[1].因此,本研究探讨bFGF在腹膜组织新牛血管形成中可能的作用及机制.     

Expression of basic fibroblast growth factor and its receptor in the progression of rat crescentic glomerulonephritis

Summary: The aim of this study was to examine the relationship of basic fibroblast growth factor (FGF-2) and its receptor (FGF-R) to tubular proliferation, interstitial fibrosis, glomerular cell proliferation and crescent formation in the development of anti glomerular basement membrane (GBM) glomerulonephrids in the rat. Using new microwave-based histochemistry techniques, weak constitutive expression of mRNA and protein for FGF-2 and FGF-R was evident in tubules and glomeruli of normal rat kidney. Double and triple staining with the proliferating cell nuclear antigen (PCNA) demonstrated that in disease there was focal up-regulation of FGF-2 and FGF-R mRNA and protein expression within proliferating tubules and fibroblast-like cells in areas of interstitial fibrosis. In contrast, tubules in non-inflamed areas of kidney showed no change in FGF-2 and FGF-R expression or cellular proliferation. In addition, many FGF-2⁺PCNA⁺ and FGF-R⁺PCNA⁺ cells, probably mesangial cells and podocytes, were evident within glomerular segmental proliferative lesions. of particular interest was the observation that many epithelial cells within cellular crescents, inculding proliferating (PCNA⁺) epithelial cells, strongly expressed both FGF-2 and FGF-R. Furthermore, there was strong FGF-2 and FGF-R expression by proliferating fibroblast-like cells within fibrocellular crescents suggesting that FGF-2 is involved in the formation and fibrotic progression of glomerular crescents. In conclusion, this study provides evidence that increased expression of FGF-2 and its receptor may participate in the proliferative/fibrotic response in progressive crescentic glomerulonephritis.     

碱性成纤维细胞生长因子对成骨细胞中转化生长因子-β1和碱性成纤维细胞生长因子mRNA表达的影响

目的　探讨外源性碱性成纤维细胞生长因子 (bFGF)对体外成骨细胞中的生长因子 :转化生长因子 β1 (TGF β1 )和bFGFmRNA表达的影响。 方法　将体外培养的新生SD大鼠颅骨成骨细胞 ,用不同浓度的bFGF(5～ 50 μg/L)进行处理 ,利用核酸原位分子杂交 ,检测两种生长因子在细胞中mRNA的表达。结果　依bFGF浓度的增加成骨细胞内TGF β1mRNA表达分别是对照组的 1 .5、1 .6、1 .9和 2 .0倍 ;bFGFmRNA表达则分别是对照组的 1 .2 8、1 .37、1 .40和 1 .51倍。bFGF组中 ,TGF β1和bFGFmRNA的表达量均明显高于对照组 (P <0 .0 1 )。结论　外源性bFGF可以对成骨细胞自分泌bGFG产生影响 ,还能够促进TGF β1的合成