BACKGROUNDMyopia is a common disorder and the incidence has increased yearly, but its pathogenesis remains unclear. The aim of this study was to investigate the possible role of hepatocyte growth factor (HGF) and its receptor c-Met in the development of lens-induced myopia in guinea pigs.

METHODSSixty one-week-old guinea pigs were chosen. The right eyes were treated with -10.0 diopters (D) lenses as the lens-induced myopia group; the left eyes remained untreated as the control group. Six weeks later, refractive status and axial length were determined by streak retinoscopy and A-scan ultrasonography, respectively. The guinea pigs were killed and both eyes collected. Morphological changes were observed by hematoxylin and eosin staining. The expression levels of HGF, c-Met, and matrix metalloproteinase 2 (MMP-2) mRNA and protein in the posterior sclera were analyzed by RT-PCR and Western blotting, respectively.

RESULTSThe lens-induced myopia group became myopic with a significant increase in axial length and a significant decrease in refraction. Compared with the control group, the posterior retina and sclera were thinner in the lens-induced myopia group. The expression levels of HGF and MMP-2 mRNA and protein and of phosphorylated c-Met protein were significantly higher in the posterior sclera of the lens-induced myopia group than in the control group (all P < 0.05). In the lens-induced myopia group, the expression level of MMP-2 in the posterior sclera positively correlated with the expression level of HGF (r = 0.902, P < 0.05) and phosphorylated c-Met (r = 0.885, P < 0.05).

CONCLUSIONHGF/c-Met might play a role in the development of lens-induced myopia in guinea pigs by upregulating the expression of MMP-2.

Animals ; Guinea Pigs ; Hepatocyte Growth Factor ; metabolism ; Myopia ; etiology ; metabolism ; Proto-Oncogene Proteins c-met ; metabolism

Animals ; Estradiol ; blood ; pharmacology ; Hepatocyte Growth Factor ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar

Animals ; Hepatocyte Growth Factor ; metabolism ; Humans ; Proto-Oncogene Proteins c-met ; Serine Endopeptidases

OBJECTIVETo explore the effect of tacrolimus on murine hair follicle cycle.

METHODHematoxylin-eosin dyeing and reverse transcription-polymerase chain raction techniques were used.

RESULTSFive days after depilation, the hair follicles in both the tacrolimus group and the minoxidil group was in anagen V, while that in the vaseline group was in anagen III. vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were detected in back skin in both the tacrolimus group and the minoxidil group, but not in the vaseline group.

CONCLUSIONTacrolimus can promote the growth of hair by stimulating the hair follicle to enter anagen V in mice, which may be explained by the effects of VEGF and HGF.

Animals ; Hair Follicle ; drug effects ; physiology ; Hepatocyte Growth Factor ; metabolism ; Mice ; Mice, Inbred C57BL ; Minoxidil ; pharmacology ; Skin ; drug effects ; metabolism ; Tacrolimus ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUND: Hemoglobin concentration reportedly is positively associated with muscle strength, for example, handgrip strength. However, hemoglobin cannot repair muscle directly, but is beneficial only in a supportive role. Since hepatocyte growth factor (HGF) regulates muscle satellite cell production and differentiation, which is stimulated by organ injury, the supportive effect of hemoglobin should thus be stronger for participants with high HGF than for those with low HGF. However, the association between hemoglobin concentration and handgrip strength in relation to HGF levels remains unknown. METHODS: We conducted a cross-sectional study of 255 Japanese elderly men aged 60-69 years who participated in annual health check-ups in 2014-2015. The study population was categorized on the basis of a median value of HGF of 300.6 pg/mL. RESULTS: Among present study population, 128 participants showed low HGF. For participants with low HGF, hemoglobin concentration showed no significant association with handgrip strength (standardized parameter estimate (β) = 0.03, p = 0.767), but for those with high HGF, hemoglobin concentration was significantly positively associated with handgrip strength (β = 0.23, p = 0.014). CONCLUSIONS A significant positive association between hemoglobin level and handgrip strength was established for elderly Japanese men aged 60-69 years with high HGF but not for participants with low HGF. Our finding indicates that HGF levels could determine the relationship of hemoglobin concentration with handgrip strength in elderly Japanese men aged 60-69 years. This result can be expected to serve as an effective tool for the clarification of the roles played by HGF and hemoglobin concentration in maintenance of muscle strength.
Aged ; Cross-Sectional Studies ; Hand Strength ; physiology ; Hemoglobins ; metabolism ; Hepatocyte Growth Factor ; genetics ; metabolism ; Humans ; Japan ; Male ; Middle Aged

OBJECTIVETo study the effect of insulin in different concentrations on secretion function of growth factors of adipose-derived stem cells (ADSCs).

METHODSADSCs were isolated from human abdominal adipose tissue and cultured. The immunophenotype and adipose induced-differentiation were identified, and the third generation cells were collected. The collected cells were assigned to 1 x 10(-8), 1 x 10(-7), 1 x 10(-6) mol/L insulin groups according to the concentration of added insulin. When cells grew into 70% confluence in conventional medium, ADSCs were cultured further in serum-free DMEM containing insulin in different concentrations for 3 days. ADSCs cultured in medium without insulin were used as control group. Secretion amount of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) of ADSCs were determined by enzyme-linked immunosorbent assay. The effects of the supernatant fluid of ADSCs' nutrient solution on the proliferation and collagen synthesis of the cultured fibroblast were detected by MTT chromatometry and hydroxyproline chromatometry.

RESULTSThe secretion amounts of VEGF and HGF of ADSCs in 1 x 10(-8) and 1 x 10(-7) mol/L insulin groups [(471 +/- 41, 762 +/- 66 ng/L), (643 +/- 64, 930 +/- 67 ng/L), respectively] were significantly higher as compared with those in control group (286 +/- 47, 577 +/- 84 ng/L) (P < 0.05 or P < 0.01). No change occurred in the secretion amount of VEGF and HGF of ADSCs in 1 x l0(-6) mol/L insulin group (P > 0.05). The supernatant fluid of ADSCs' nutrient medium of 1 x 10(-8), 1 x 10(-7) mol/L insulin groups showed obvious stimulative effect on the proliferation and collagen synthesis of fibroblasts, and it was most obvious in the 1 x 10(-7) mol/L group (P < 0.05 or P < 0.01).

CONCLUSIONSInsulin in the concentrations of 1 x 10(-8) and 1 x 10(-7) mol/L can notably promote ADSCs' function of secreting VEGF and HGF.

Adipocytes ; cytology ; drug effects ; secretion ; Cells, Cultured ; Fibroblasts ; cytology ; Hepatocyte Growth Factor ; metabolism ; Humans ; Insulin ; pharmacology ; Stem Cells ; cytology ; drug effects ; secretion ; Vascular Endothelial Growth Factor A ; metabolism

AIMTo construct a plasmid carrying hepatocyte growth factor gene and investigate its effects in vitro.

METHODSA complementary DNA (cDNA) clone for human HGF was isolated from human placental cDNA, then subcloned into pUDK vector, which was constructed by ourselves, to form the pUDKH plasmid. The transfection efficiency and the expression level of HGF and VEGF were evaluated by transfecting pUDK or pUDKH into primary rat skeletal muscle cells. The biological effects of HGF-expressing product at different doses on endothelial cells were investigated in vitro, and assessed by MTT.

RESULTSThe primary rat skeletal muscle cells could be transfected efficiently with pUDKH (0.057%), and secreted HGF(16 -18 ng/4 x 10(5) cells) and VEGF proteins. The expressing product could significantly stimulate proliferation of human umbilical vein endothelial cells, in a dose-dependent manner (P < 0.05).

CONCLUSIONpUDKH has the potential application in vivo to treat ischemic diseases.

Animals ; Cells, Cultured ; DNA, Complementary ; genetics ; Genetic Vectors ; Hepatocyte Growth Factor ; genetics ; metabolism ; Humans ; Plasmids ; Rats ; Rats, Wistar ; Transfection

OBJECTIVETo obtain high expression of human hepatocyte growth factor (HGF) in passaged rabbit bone marrow-derived mesenchymal stem cells (BMSCs) via recombinant adenovirus vector mediated HGF gene transfection, and explore the feasibility of this strategy for local treatment of avascular necrosis of the femoral head (ANFH).

METHODSHGF gene was subcloned into the adenovirus shuttle plasmid pDC316, and the products were co-transfected into HEK293 cells with the helper plasmid pBHGlox deltaE1,3Cre. The recombinant adenovirus Ad-HGF was generated by homologous recombination of the 2 plasmids in HEK293 cells. After PCR identification, Ad-HGF was amplified and purified and its titer measured by TCID50 assay before transfected into the second passage of rabbit BMSCs. The transcription and expression of HGF gene in the transfected BMSCs was detected by RT-PCR, in situ hybridization, and immunological histochemistry.

RESULTSAd-HGF was successfully constructed with a titer of 2.6x10(10) TCID50/ml. The expressions of HGF mRNA and protein were confirmed in the transfected BMSCs.

CONCLUSIONAd-HGF transfection allows efficient expression of HGF protein in rabbit BMSCs, and this success may facilitate further study of local treatment of ANFH using HGF-expressing BMSCs.

Adenoviridae ; genetics ; Animals ; Cell Line ; Genetic Vectors ; Hepatocyte Growth Factor ; biosynthesis ; genetics ; Humans ; Mesenchymal Stromal Cells ; metabolism ; Rabbits ; Transfection

OBJECTIVETo explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts.

METHODSCongestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization.

RESULTSTen weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too.

CONCLUSIONAutologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.

Animals ; Disease Models, Animal ; Heart Failure ; metabolism ; therapy ; Hepatocyte Growth Factor ; metabolism ; Insulin-Like Growth Factor I ; metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transplantation, Autologous ; Vascular Endothelial Growth Factor A ; metabolism ; Ventricular Remodeling

OBJECTIVETo study the expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) in kidney tissues of children with primary focal segmental glomerular sclerosis (FSGS) and the possible role of the two growth factors in the development of FSGS.

METHODSKidney specimens were obtained from 33 children with primary FSGS and 7 children with isolated haematuria but without FSGS (control group). Of the 33 children with primary FSGS, 6 children had no renal tubule interstitial pathological damage (Experimental I group) and 27 children had renal tubule interstitial pathological damage (Experimental II group). Expression of TGF-beta and HGF in kidney tissues was ascertained by the immunohistochemical method.

RESULTSTGF-beta and HGF were expressed in the three groups, but there were significant differences among the three groups. The expression of TGF-beta and HGF in the two experiment groups increased significantly compared with that in the control group. The Experimental II group had increased TGF-beta expression but a significantly decreased HGF expression compared with the Experimental I group. The index of tubule interstitial pathological changes was positively correlated with the TGF-beta expression (r=0.763, P<0.01), but negatively correlated with the HGF expression (r=-0.461, P<0.05) in the Experimental II group. There was a negative correlation between TGF-beta and HGF expression in children with primary FSGS (r=-0.425, P<0.05).

CONCLUSIONSThe expression of TGF-beta and HGF in kidney tissues is increased in children with primary FSGS. TGF-beta might be a fibrogenic factor and HGF might be an anti-fibrotic factor in the kidney in primary FSGS.

Child ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Hepatocyte Growth Factor ; analysis ; Humans ; Immunohistochemistry ; Kidney ; chemistry ; Kidney Tubules ; pathology ; Transforming Growth Factor beta ; analysis