The protein expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) channel, in ovarian stimulated premature female rat ovary during a cycle of follicle development and corpus luteum formation was investigated. Animals were injected with 10 U pregnant Mare's serum gonadotropin (PMSG) and subsequently 10 U hCG 48 h later. Time-dependent immunohistochemistry and Western blotting experiments were performed before and 24, 48, 72 h after hCG treatment. The immunohistochemistry revealed that administration of PMSG stimulated the CFTR expression in thecal cell layer and granulosa cell layer of mature follicles 48 h post injection, coincident with the PMSG-induced peak in follicular estradiol. However, the expression of CFTR in the granulose lutein cell layer and thecal lutein cell layer was time-dependently reduced following hCG injection, in accordance with the gradually increased progestogen level during luteum corpus formation. Western blotting analysis demonstrated that rat ovarian tissue expressed the special CFTR band at 170 kD. It is concluded that cAMP-dependent Cl(-) channels are involved in regulation of follicle development and luteum formation.
Connective Tissue Growth Factor/genetics ; Connective Tissue Growth Factor/*metabolism ; Connective Tissue Growth Factor/*physiology ; Corpus Luteum/growth & development ; Ovarian Follicle/growth & development ; Ovary/*metabolism ; Rats, Wistar

Connective Tissue Growth Factor ; Humans ; Myocardial Infarction ; physiopathology ; Ventricular Remodeling

The insulin-like growth factor binding protein (IGFBP) family is a critical component of the insulin-like growth factor (IGF) system which regulate the biological actions of the IGFs and may also be capable of IGF-independent actions. To date, seven distinct IGFBPs have been described. Among these IGFBPs, IGFBPs-1-6 bind IGFs with high affinity, while only IGFBP-7 binds with low affinity. Recently, we have demonstrated that connective tissue growth factor (CTGF) also binds IGFs with low affinity, suggesting that a family of low-affinity IGFBPs, distinct from the high-affinity members, may exist, and together these constitute an IGFBP superfamily. IGFBPs have various biological roles. IGFBPs act not only as a carrier proteins, but also as a modulators of IGF actions by involving in IGF ligand-receptor interactions through influences on both the bioavailability and distribution of IGFs in the extracellular environment. In addition, some IGFBPs (IGFBPs-1, -3, and -5) appears to have intrinsic activity independent of IGFs. This review will focus on recent studies on the biological roles of IGFBPs in IGF-dependent and IGF-independent modes.
Biological Availability ; Carrier Proteins ; Connective Tissue Growth Factor ; Humans ; Insulin-Like Growth Factor Binding Proteins* ; Somatomedins

Adult wounds heal with scar formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. Recently connective tissue growth factor (CTGF) is known to play an important role in wound healing. We reasoned that a strategy employing antisense oligodeoxynucleotides (ODN) complementary to CTGF mRNA by topical application of the ODN on the skin wound. Phosphorothioation of ODN to retard their degradation. When antisense CTGF ODN were applied on the wound site, there was a marked reduction of scarring compared with a control wound site. This effect of antisense CTGF ODN on scar forrnation was associated with decreased expression of the CTGF gene. However, sense CTGF ODN had no effect on the expression of the CTGF gene. In addition, control wounds healed with excessive fibrosis compared with the antisense-treated wounds. In conclusion, our results indicate that antisense CTGF ODN could be used for ameliorating scar formation during wound healing.
Adult* ; Cicatrix* ; Connective Tissue Growth Factor* ; Connective Tissue* ; Fibrosis ; Humans ; Oligodeoxyribonucleotides ; RNA, Messenger ; Skin ; Wound Healing ; Wounds and Injuries*

Skin fibrotic disorders are understood to develop under the influence of various cytokines, such as transforming growth factor(TGF)-beta1, connective tissue growth factor(CTGF) and vascular endothelial growth factor (VEGF). To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, the author investigated the in vivo effects of growth factors by injecting recombinant TGF-beta1 protein and pCMV- Flag5-CTGF into the subcutaneous tissue of Sprague- Dawley rats. A single application of TGF-beta1 protein and CTGF DNA resulted in the formation of transient granulation tissue. Immunohistochemical finding showed increased expression of TGF-beta1 protein after injection of pCMV-Flag5-CTGF. In situ hybridization analysis revealed the expression of CTGF mRNA after injection of TGF-beta1 protein. VEGF expression was not affected by the TGF-beta1 and CTGF injection. These findings suggest TGF-beta1 and CTGF are deeply related with skin fibrosis and it appears that TGF-beta1 may cause the induction of CTGF expression. The animal model on skin fibrosis by exogenous application of TGF-beta1 protein and CTGF DNA developed in this study may be useful for future studies on fibrotic disorders.
Animals ; Cicatrix* ; Connective Tissue ; Connective Tissue Growth Factor ; Cytokines ; DNA ; Fibrosis ; Granulation Tissue ; In Situ Hybridization ; Intercellular Signaling Peptides and Proteins ; Models, Animal ; Rats* ; RNA, Messenger ; Skin ; Subcutaneous Tissue ; Transforming Growth Factor beta1* ; Vascular Endothelial Growth Factor A*

PURPOSE: To evaluate the effect of a preoperative subconjunctival injection of mitomycin C or triamcinolone in patients with recurrent pterygium. METHODS: The records of 50 eyes of 50 patients who received excision of recurrent pterygium between June 2006 and January 2007 were reviewed. The recurrence rate and postoperative fibrovascular growth were compared in the preoperative subconjunctival mitomycin C, or triamcinolone injection group and non-treated control group. Additionally, the quantitative expression level of the transforming growth factor-beta1, -beta2 (TGF-beta1, -beta2), connective tissue growth factor (CTGF), and vascular endothelial growth factor (VEGF) in excised sample of the pterygium was assessed. RESULTS: There was no statistically significant difference in the recurrence rate and the relative gene expression level of growth factors in the triamcinolone group and the mitomycin group when compared with the non-treated control group. Postoperative fibrovascular proliferation was more severe in the triamcinolone group than other groups. CONCLUSIONS: Subconjunctival mitomycin C or triamcinolone as adjunctive therapy before pterygium excision did not influence the recurrence rate of pterygium.
Connective Tissue Growth Factor ; Eye ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; Mitomycin ; Pterygium ; Recurrence ; Triamcinolone ; Vascular Endothelial Growth Factor A

Proliferative vitreoretinal disorders are characterized by an intravitreal and periretinal migration of RPE(retinal pigment epithelial) cells that form a scar-like contractile connective tissue. It has been reported that TGF(transforming growth factor)beta is a key cytokine that initiates and terminates tissue repair and whose sustained production underlies the development of tissue fibrosis.In the current study, we investigated the effects of TGFbeta on RPE-mediated vitreous gel contraction. TGFbetaeffecs on DNA synthesis in RPE cells were assessed by 3H-thymidine incorporation. The contraction of vitreous gel by TGFbeta treated RPE cells were evaluated by the decrease of gel weight. TGFbeta inhibited the proliferation of RPE cells. Once RPE cells were placed onto vitreous, they changed their morphology and became fibroblast-like cells. When RPE cells were incubated with TGFbeta1 and TGFbeta2, the vitreous contractin effect of RPE cells was enhanced significantly. This study suggests that TGFbeta1 and TGFbeta2 enhance the scar contraction. But TGFbeta3 may have the anti-scar contraction effect.
Cicatrix ; Connective Tissue ; DNA ; Retinal Pigment Epithelium ; Transforming Growth Factor beta*

Connective Tissue Growth Factor ; metabolism ; Epithelial-Mesenchymal Transition ; Hepatocytes ; cytology ; Humans ; Liver ; pathology ; Liver Cirrhosis ; pathology

OBJECTIVE: To detect the relationship between CTGF in the bone marrow of MM patients and osteolytic lesion of myeloma, moreover, to investigate the clinical significance of CTGF in MM. METHODS: Fifity-four MM patients treated in our hospital from March 2019 to April 2020 were enrolled, and 28 healthy volunteers were selected as the control group. The plasma in bone marrow of the patients was collected, and the ELISA was used to detect the level of CTGF in bone marrow plasma and the relationship between its and clinical characteristics were statistically analyzed. RESULTS: The CTGF level of MM patients was significantly higher than those in the healthy control group (P<0.001); the CTGF level in male patients was higher than that in female patients (P=0.007); the CTGF level in MM patients with osteolytic lesions was significantly higher than patients without osteolytic lesions and controls (P=0.007, P=0.001). The CTGF level in MM patients was positively correlated with the number of bone lesions (P<0.001, r=0.52). CTGF levels in patients with ≥3 bone lesions were significantly higher than those with <3 bone lesions and without bone lesions (P=0.014, P=0.002). ROC curve result showed that CTGF expression level shows a significant diagnostic value for MM bone disease (P<0.001). CONCLUSION The abnormally high expression of CTGF level in MM patients is related to the degree of myelomas osteolytic lesions and can reflect the progress of MM.
Bone Marrow ; Connective Tissue Growth Factor ; Female ; Humans ; Male ; Multiple Myeloma ; Osteolysis ; Patients ; ROC Curve

OBJECTIVE: To investigate the changes in serum levels of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) in patients with atrial fibrillation (AF) and their value for predicting recurrence of AF after radiofrequency ablation (RFCA). METHODS: Sixty-six patients with paroxysmal AF (PaAF) and 72 with persistent AF (PaAF) admitted in our hospital were recruited as AF group and 80 patients with sinus rhythm as the control group, and in all the participants, serum levels of ET-1 and CTGF were measured using ELISA and Western blotting. From 6 patients with AF and 6 with sinus rhythm undergoing cardiac surgery in our hospital, tissue samples of the right atrial appendage were taken intraoperatively for observation of structural changes of the cardiomyocytes, myocardial fibrosis and expression of ET-1 and CTGF protein. In AF group, the patients receiving RFCA were followed up for 6 months following the procedure for assessment of the outcomes. RESULTS: Compared with the control patients, the patients with AF showed obvious damages of the cardiomyocyte structure and myocardial fibrosis. Serum levels of ET-1 and CTGF levels were significantly higher in PaAF and PeAF groups than in the control group, and were higher in PeAF group than in PaAF group. In the patients with AF, serum ET-1 and CTGF levels were positively correlated with left atrial diameter (LAD) (P < 0.05), and ET-1 was positively correlated with CTGF levels (P < 0.05). In patients with postoperative AF recurrence, the serum levels of ET-1 and CTGF were significantly higher than those in patients without recurrence; serum ET-1 and CTGF levels before and after the operation were positively correlated with the recurrence of PeAF, and elevated serum levels of ET- 1 and CTGF were identified by logistic regression analysis as independent risk factors for postoperative recurrence of PeAF. CONCLUSION Serum levels of ET-1 and CTGF are significantly elevated in AF patients in positive correlation with AF duration. ET-1 and CTGF levels are higher in AF patients with postoperative recurrence, and they both have predictive value for recurrence of PeAF following RFCA.
Humans ; Atrial Fibrillation ; Endothelin-1 ; Connective Tissue Growth Factor ; Chronic Disease ; Atrial Appendage ; Fibrosis