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Biomedical subjects

X Meng

Publications and source records attributed to X Meng.

At least 163 records · Page 9Linked to original sources
PubMed1997

Cardioadaptation induced by cyclic ischemic preconditioning is mediated by translational regulation of de novo protein synthesis.

Repetitive episodes of brief ischemia induce myocardial adaptation to prolonged ischemia. To investigate whether this myocardial adaptive response involves gene transcription and de novo protein synthesis, this study examined the effects of actinomycin D (ActD) and cycloheximide (Chx) on the cardioprotection induced by repeated ischemic preconditioning. Isolated, perfused working rat hearts underwent cyclic ischemia (CI, four 5-min ischemic intervals, 37 degrees C) with and without pretreatment with Chx (1.0 mg/kg, ip; translation inhibition) or ActD (1.5 mg/kg, ip; transcription inhibition) 3 hr prior to heart isolation. All hearts were subjected to 20 min global ischemia (37 degrees C) and 40 min reperfusion (I/R). Coronary effluent was assayed for creatine kinase (CK) activity. Myocardial tissue was homogenized and crude protein content determined. CI preconditioning improved postischemic recovery of cardiac output (CO; 48 +/- 5.1% vs 73 +/- 2.8% for control and CI, respectively, P < 0.05) and reduced CK release (61 +/- 8.5 U/L vs 38 +/- 4.2 U/L for control and CI, respectively, P < 0.05). The beneficial effects of CI preconditioning on myocardial function and cellular integrity were abolished by Chx while ActD had no effect. Myocardial protein content was increased in CI preconditioned myocardium relative to control hearts (5082 +/- 89 microg/g vs. 4459 +/- 260 microg/g, respectively, P < 0.05). Similarly, pretreatment with Chx but not ActD prevented the increase in myocardial protein content (Chx + CI, 4020 +/- 254 microg/g; ActD + CI, 5049 +/- 68 microg/g, P < 0.05 Chx + CI vs CI or ActD + CI). Myocardial dry/wet weight ratios were not different between groups (P > 0.05). We conclude that CI preconditioning induces protein synthesis-dependent myocardial protection against I/R injuries. CI-induced de novo protein synthesis in the myocardium appears to be regulated at the translational level rather than by gene transcription.

Adaptation, Physiological↗
PubMed1997

A keratin K10 gene mutation in a Japanese patient with epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis (EHK), or bullous congenital ichthyosiform erythroderma, is characterized by generalized erythroderma, ichthyosiform skin and blistering, and is caused by an aberration of the keratin intermediate filaments. In this study, we examined keratin K10 and 1 gene mutations in a Japanese EHK patient who had severe ichthyosiform erythroderma at birth and developed subsequent blistering. The patient had a G to A transition at codon 156 of the keratin K10 gene, which resulted in an arginine (Arg)-->histidine (His) substitution in the helix initiation peptide of the highly-conserved 1A domain in keratin K10. This is the first mutation report of a Japanese patient with EHK, although the position and mode of the mutation identified here did not differ from those in reported Western cases.

Amino Acid Sequence↗
PubMed1997

Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds.

Adult↗
PubMed1997

Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation.

Adenosine↗
PubMed1997

Nitric oxide synthase is not involved in cardiac contractile dysfunction in a rat model of endotoxemia without shock.

Endotoxin and proinflammatory cytokines induce nitric oxide synthase (NOS), and nitric oxide (NO) plays an important role in promoting endotoxin shock. However, the role of NOS in endotoxemic cardiac contractile dysfunction is not defined. To determine whether endotoxemic cardiac contractile dysfunction involves NOS, the present study used a rat model of endotoxemia without shock and examined the effects of glucocorticoids (dexamethasone, a potent inhibitor of inducible NOS, iNOS, expression), isoform nonselective NOS inhibitor (NG-monomethyl-L-arginine, L-NMA) and iNOS selective inhibitor (S-methylisothiourea sulfate, SMT) on cardiac contractile dysfunction. A sublethal dose of endotoxin (from Salmonella typhimurium, .5 mg/kg, i.p.) was given to adult rats, and left ventricular developed pressure (LVDP) examined by Langendorff technique was attenuated in hearts isolated at 4 or 6 h (66.7 +/- 3.4 and 60.3 +/- 5.5 mmHg, respectively, p < .05 vs. 102 +/- 2.4 mmHg in saline control) after endotoxin treatment. Pretreatment of rats with dexamethasone (4.0 mg/kg, i.v., -30 min) partially abolished endotoxin-induced contractile dysfunction at 6 h (LVDP 87.6 +/- 6.8 mmHg, p < .05 vs. endotoxin alone at 6 h). However, pretreatment with L-NMA (30 mg/kg, i.v., -5 min) or SMT (5.0 mg/kg, i.v., -1 min) failed to prevent the contractile dysfunction. Moreover, infusion of L-NMA or SMT in vitro could not restore contractile function in hearts isolated at 6 h after endotoxin treatment. In contrast, inhibition of NOS with L-NMA or SMT in vitro further attenuated coronary flow in endotoxin-treated hearts. Thus, endotoxemic cardiac contractile dysfunction in this non-shock rat model may not involve NOS, and inhibition of NOS may deteriorate coronary perfusion in endotoxemic heart.

Animals↗
PubMed1997

Endotoxin stuns cGMP-mediated pulmonary vasorelaxation.

Net pulmonary vascular tone is determined by the balance of pulmonary vasorelaxation and vasoconstriction. In endotoxemic rats, cGMP-mediated pulmonary vasorelaxation is impaired through neutrophil-dependent mechanisms, yet agonist stimulated vasoconstriction remains intact. Endotoxin-induced lung neutrophil accumulation is a transient response. In models of myocardial ischemia-reperfusion injury, "stunning" or reversible cardiac dysfunction is also associated with a reversible neutrophil presence. We hypothesized that lung neutrophil accumulation and dysfunction of cGMP-mediated pulmonary vasorelaxation is reversible after an endotoxin challenge. Our purpose was to examine lung neutrophil accumulation and endothelium-dependent and -independent mechanisms of cGMP-mediated pulmonary vasorelaxation 4 and 48 h after endotoxin challenge. Rats (n = 5 per group) were studied 4 and 48 h after injection of saline or endotoxin (500 micrograms/kg, intraperitoneal). Endothelium-dependent relaxation by receptor-dependent (acetylcholine) and -independent (A23187) mechanisms and endothelium-independent (sodium nitroprusside) relaxation were studied in isolated pulmonary artery rings preconstricted with phenylephrine. Lung neutrophil accumulation was examined by lung myeloperoxidase assay. Lung neutrophil accumulation was increased at 4 h (p < .05 vs. control) and was attenuated by 48 h (p < .05 vs. endotoxin x 4 h) following endotoxin challenge. Similarly, the endotoxin-induced dysfunction of endothelium-dependent and -independent cGMP-mediated pulmonary vasorelaxation at 4 h normalized by 48 h. Endotoxin appears to induce reversible dysfunction of pulmonary vasorelaxation through stunning of vascular endothelial and smooth muscle cells.

Acetylcholine↗
PubMed1997

In vivo transfer of a foreign gene to keratinocytes using the hemagglutinating virus of Japan-liposome method.

The hemagglutinating virus of Japan (HVJ)-liposome method involves the entrapment of DNA and nuclear protein within liposomes and the use of HVJ to enhance liposome fusion with cell membranes. This method has been used successfully for in vivo gene transfer to various types of tissue. In this study, we investigated whether this method transfers genes effectively to normal and malignantly transformed keratinocytes in vivo. We applied HVJ-liposome complex (HLC) containing the beta-galactosidase gene to the tape-stripped skin of hairless rats and detected the enzyme activity in the keratinocytes of the treated skin. Comparison of this method with the naked DNA injection method, which was shown recently to be useful for in vivo gene transfer to keratinocytes, demonstrated that the transfer efficiency of the latter was about 5 times higher than that of the former. We assessed the efficacy of the HVJ-liposome method for gene transfer to transformed keratinocytes by examining the effect of HLC containing the herpes simplex virus thymidine kinase gene on the growth of mouse squamous cell carcinomas. Local injection of HLC into the tumors followed by administration of ganciclovir to mice resulted in tumor growth inhibition. These results indicate that the HVJ-liposome method is suitable for in vivo gene transfer to keratinocytes; also that this method may prove a good tool for basic research into keratinocyte biology and future keratinocyte gene therapy.

Animals↗
PubMed1997

Characterization of a neurotoxigenic Clostridium butyricum strain isolated from the food implicated in an outbreak of food-borne type E botulism.

Neurotoxigenic Clostridium butyricum was isolated from the food implicated in an outbreak of clinically diagnosed type E botulism in China. PCR assay showed that the isolate (LCL 155) contained the type E botulinum toxin gene. This appears to be the first report of neurotoxigenic C. butyricum causing food-borne botulism.

Bacteriological Techniques↗
PubMed1997

LPS-induced delayed myocardial adaptation enhances acute preconditioning to optimize postischemic cardiac function.

Myocardial tolerance to ischemia and reperfusion (I/R) injury can be achieved by either acute or delayed cardioprotective mechanisms. Ischemic preconditioning has been demonstrated to be a powerful acute cardioprotective stimulus. We have reported that lipopolysaccharide (LPS) pretreatment induces delayed myocardial adaptation to I/R injury. To optimize myocardial protection, we examined the ability of delayed myocardial adaptation to enhance acute ischemic preconditioning in the isolated working rat heart. Male Sprague-Dawley rats were divided into control, acute [transient ischemia (TI); 5-min global ischemia, 37 degrees C], delayed (LPS; 500 micrograms/kg i.p.), or combined (LPS + TI) cardioprotective groups. Delayed cardioprotection involved LPS injection 72 h before heart isolation. All hearts were subjected to 20-min global ischemia (37 degrees C) and 30-min reperfusion. Coronary effluent collected during reperfusion was assayed for creatine kinase (CK) activity. Both TI and LPS treatment improved postischemic aortic flow recovery (29 +/- 4.5 and 44 +/- 4.0%, respectively; P < 0.05, LPS vs. TI) compared with control hearts (11 +/- 2.2%; P < 0.05, TI or LPS vs. control). When TI was applied to LPS-treated hearts (LPS + TI), aortic flow recovery was further enhanced (57 +/- 3.8%; P < 0.05 vs. TI or LPS alone). CK release during 20 and 30 min of reperfusion was decreased in all treated hearts compared with control hearts (P < 0.05). These results indicate that delayed myocardial adaptation and acute ischemic preconditioning independently activate protective mechanisms against ischemia. Enhanced protection occurs when induced delayed mechanisms are combined with acute cardioprotective stimuli, which optimize postischemic myocardial function and reduce myocellular necrosis.

Adaptation, Physiological↗
PubMed1997

Early and delayed preconditioning: differential mechanisms and additive protection.

The purposes of this study were to determine whether 1) 24-h endotoxin (ETX) pretreatment induces delayed ("second window") myocardial protection against ischemia-reperfusion (I/R), 2) acute adenosine (Ado) or phenylephrine (PE) pretreatment confers similar protection, 3) the mechanisms of Ado- and PE-induced early protection remain intact after endotoxemia, 4) Ado- and PE-induced protection may combine with ETX-induced delayed protection to optimize cardiac protection, and 5) these strategies of early and/or delayed myocardial protection require de novo protein synthesis. Rats (n = 6-8/group) were treated with ETX (0.5 mg/kg i.p.) or vehicle, with or without prior inhibition of protein synthesis. Twenty-four hours later, the hearts were isolated, perfused, and acutely pretreated with Ado or PE before I/R (20-min ischemia and 40-min reperfusion). Developed pressure, coronary flow, compliance (end-diastolic pressure), and reperfusion creatine kinase leak were measured. Results indicated that 1) Ado, PE, and ETX independently induced myocardial functional protection; 2) either Ado or PE acutely enhanced ETX induced protection; and 3) cycloheximide abolished delayed, but not acute, protection. We conclude that early and delayed forms of protection 1) may be combined to optimize protection and 2) differentially rely on de novo protein synthesis.

Adenosine↗
PubMed1997

Ischemic preconditioning of human myocardium: protein kinase C mediates a permissive role for alpha 1-adrenoceptors.

The purposes of this study were to determine whether ischemic preconditioning (IPC) in human atrial trabeculae is mediated by alpha 1-adrenoceptors and protein kinase C (PKC) and whether the protection of IPC is replicated with alpha 1-adrenoceptor stimulation [alpha 1-adrenoceptor preconditioning (alpha 1-PC)]. Atrial trabeculae were obtained during coronary bypass surgery. The trabeculae were suspended in organ baths containing Tyrode solution and field stimulated at 1 Hz, and developed force was recorded. The trabeculae underwent 45 min of simulated ischemia (SI) and 120 min of reperfusion (I/R injury). IPC trabeculae received transient SI before I/R injury, alpha 1-Adrenoceptor blockade with BE-2254 and PKC inhibition with chelerythrine were independently combined with IPC before I/R injury. alpha 1-PC before I/R was examined with alpha 1-adrenergic agonist (phenylephrine) pre-treatment. Improved recovery of developed force and higher tissue creatine kinase activity were present in IPC trabeculae, and the protective effect of IPC was eliminated with either alpha 1-adrenoceptor blockade or PKC inhibition. alpha 1-PC trabeculae also exhibited enhanced functional recovery after I/R injury but lacked preservation of tissue creatine kinase activity. PKC inhibition eliminated the functional protection of alpha 1-PC. These results suggest that, in human atrial trabeculae, alpha 1-adrenoceptors and PKC mediate, in part, the functional and tissue CK preservation conferred by IPC, but alpha 1-PC does not replicate the protection of IPC.

Creatine Kinase↗
PubMed1997

LPS induces late cardiac functional protection against ischemia independent of cardiac and circulating TNF-alpha.

Lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha independently induce cardioprotection against ischemia in the rat at 24 h after administration, suggesting that endogenously synthesized TNF-alpha may play a role in LPS-induced protection. The purposes of this study were 1) to delineate the time course of LPS-induced cardiac functional protection against ischemia and its relation with myocardial and circulating TNF-alpha profile, 2) to examine whether prior protein synthesis inhibition abrogates the protection, and 3) to assess the effects of TNF-alpha inhibition and neutralization on the protection. Rats were treated with LPS (0.5 mg/kg i.p.). Cardiac functional resistance to normothermic global ischemia-reperfusion was examined at sequential time points after LPS treatment in isolated hearts by the Langendorff technique. Myocardial and circulating TNF-alpha was determined by enzyme-linked immunosorbent assay at 1-24 h after LPS treatment. Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide pretreatment (0.5 mg/kg i.p. 3 h before LPS treatment). Increases in myocardial and circulating TNF-alpha preceded the acquisition of protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg i.p. 30 min before LPS treatment) abolished peak increase in myocardial TNF-alpha and substantially suppressed circulating TNF-alpha (54.3 and 85.9% inhibition, respectively) without an influence on the maximal protection. Similarly, maximal protection was not affected by TNF binding protein (40 or 80 microg/kg i.v. immediately after LPS treatment). The results suggest that LPS-induced cardiac functional protection against ischemia is a delayed and long-lasting protective response that may involve de novo protein synthesis. Although LPS-induced increase in myocardial and circulating TNF-alpha precedes the delayed protection, it may not be required for the delayed protection.

Animals↗
PubMed1997

Hemorrhage induces acute cardioadaptation to ischemia-reperfusion by an alpha1-adrenoceptor-mediated, protein synthesis-independent mechanism.

Hemorrhage and resuscitation (H-R) has been recognized as an exclusively destructive process that results in multiple organ dysfunction. Although it is well established that endogenous adaptation mechanisms exist, it is unknown whether H-R induces endogenous adaptive/protective mechanisms. Furthermore, alpha1-adrenoceptors and de novo protein synthesis have been variably implicated in myocardial adaptation responses. This study tests the hypothesis that H-R results in myocardial adaptation by a mechanism mediated by alpha1-adrenoceptors and requiring de novo protein synthesis. The aims of the present study were to determine 1) whether H-R stress results in acute cardioadaptation to subsequent global, normothermic ischemia-reperfusion (I-R); 2) whether H-R-induced endogenous adaptation is mediated by alpha1-adrenoceptors; and 3) whether H-R-induced endogenous adaptation requires de novo protein synthesis. Rats were hemorrhaged and resuscitated, sham operated, or neither, with and without prior alpha1-adrenoceptor or protein synthesis inhibition. Hearts were then isolated and subjected to a second insult consisting of global, normothermic I-R (20 min ischemia-40 min reperfusion). The results show that antecedent H-R improved post-I-R left ventricular developed pressure, compliance, coronary flow, and decreased reperfusion creatine kinase loss (P < 0.05, analysis of variance with Bonferroni-Dunn). H-R-induced adaptation was abolished by prior alpha1-adrenoceptor blockade (prazosin, 0.5 mg/kg ip); however, inhibition of de novo protein synthesis (cyclohexamide, 1.0 mg/kg ip) did not affect H-R-induced acute adaptation. This study constitutes the initial demonstration that H-R induces endogenous cardioadaptation, which is mediated by an alpha1-adrenergic signaling pathway, but does not require de novo protein synthesis.

Adaptation, Physiological↗
PubMed1997

Intrinsic membrane characteristics distinguish two subsets of nociceptive modulatory neurons in rat RVM.

Pain modulating neurons of the rostral ventromedial medulla (RVM) include three physiologically distinct classes of neurons in intact, anesthetized animals: and cells that change their activity before the onset of withdrawal reflexes and cells, which have activity unrelated to withdrawal reflexes. A previous in vitro intracellular study demonstrated that the RVM contains two types of neurons that are distinguished by their action-potential characteristics. The present in vivo intracellular study examined whether these intracellularly recorded action-potential characteristics are correlated with the physiological response properties of RVM neurons recorded. RVM neurons exhibited two distinct types of action potentials in vivo. Fast-spike (FS) neurons (n = 30) had short-duration action potentials (0.27 +/- 0.02 (SE) ms at half amplitude) and biphasic afterhyperpolarizations with a characteristic rapid overshooting spike repolarization. Slow-spike (SS) neurons (n = 25) had longer duration action potentials (0.44 +/- 0.02 ms at half-amplitude) due to a slower-spike repolarization rate and monophasic afterhyperpolarization. and cell classes included both FS and SS neurons. FS and neurons had an early onset response to noxious heat stimulation. SS and cells showed a delayed onset response to noxious heat. cells (n = 13) were all SS cells. Among the SS neurons, only cells had action potentials longer than 0. 45 ms (n = 9). FS and SS neurons were intermingled throughout the RVM. The majority of intracellularly labeled cells (n = 15) had fusiform somata with two to five fine caliber primary dendrites and a predominantly mediolateral orientation of the long axis of their dendritic tree. All labeled FS cells (n = 5) had large, multipolar somata with four to nine large caliber primary dendrites. The present study defines in vivo membrane and morphological characteristics of RVM neurons that correlate with physiological differences and may be used for identification of nociceptive modulatory RVM neurons in slice preparations.

Action Potentials↗
PubMed1997

Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo.

The initiation of mesoderm differentiation in the Drosophila embryo requires the gene products of twist and snail. In either mutant, the ventral cell invagination during gastrulation is blocked and no mesoderm-derived tissue is formed. One of the functions of Snail is to repress neuroectodermal genes and restrict their expressions to the lateral regions. The derepression of the neuroectodermal genes into the ventral region in snail mutant is a possible cause of defects in gastrulation and in mesoderm differentiation. To investigate such possibility, we analysed a series of snail mutant alleles. We found that different neuroectodermal genes respond differently in various snail mutant background. Due to the differential response of target genes, one of the mutant alleles, V2, that has reduced Snail function showed an intermediate phenotype. In V2 embryos, neuroectodermal genes, such as single-minded and rhomboid, are derepressed while ventral invagination proceeds normally. However, the differentiation of these invaginated cells into mesodermal lineage is disrupted. The results suggest that the establishment of mesodermal cell fate requires the proper restriction of neuroectodermal genes, while the ventral cell movement is independent of the expression patterns of these genes. Together with the data showing that the expression of some ventral genes disappear in snail mutants, we propose that Snail may repress or activate another set of target genes that are required specifically for gastrulation.

Amino Acid Sequence↗
PubMed1997

Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium.

The shapes of different organs can be explained largely by two fundamental characteristics of their epithelial rudiments - the pattern of branching and the rate of proliferation. Glial-cell-line-derived neurotrophic factor (GDNF) has recently been implicated in the development of metanephric ureteric epithelium (Pichel, J. G., Shen, L., Sheng, H. Z., Granholm, A.-C., Drago, J., Grinberg, A., Lee, E. J., Huang, S. P., Saarma, M., Hoffer, B.J., Sariola, H. and Westphal, H. (1996). Nature 382, 73-76; Sánchez, M.P., Silos-Santiago, I., Frisén, J., He, B., Lira, S.A. and Barbacid, M. (1996). Nature 382, 70-73; Vega, Q.C., Worby, C.A., Lechner, M.S., Dixon, J.E. and Dressler, G.R. (1996). Proc. Nat. Acad. Sci. USA 93, 10657-10661). We have analysed the target cells of GDNF and the manner in which it controls ureteric development, and have compared it with other growth factors that have been associated with the regulation of branching morphogenesis, namely hepatocyte growth factor (HGF) and transforming growth factor-beta1 (TGFbeta1). We show that GDNF binds directly to the tips of ureteric bud branches, and that it has the ability to promote primary ureteric buds from various segments of Wolffian duct and to attract ureteric branches towards the source of GDNF. It increases cell adhesion, but is not obviously mitogenic for ureteric cells. The data indicate that GDNF is required primarily for bud initiation. Comparison of GDNF, HGF and TGFbeta1 suggests that the latter act later than GDNF, and may represent a partially redundant set of mesenchyme-derived growth factors that control ureteric development. Thus, GDNF is the first defined inducer in the embryonic metanephric kidney.

Animals↗