BACKGROUND: Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, has three isoforms: TGF-beta1, TGF-beta2, and TGF-beta3. Different isoforms of TGF-beta are associated with different proliferation and differentiation states of the epidermis. Narrow band ultraviolet B (NBUVB) emits a concentrated UVB source of 311 nm. NBUVB 1,000 mJ/cm2 induces apoptosis in approximately 50% of keratinocytes. OBJECTIVE: The purpose of this study was to evaluate whether irradiation with NBUVB would alter the expression and production of TGF-beta1, 2, and 3. METHODS: We measured TGF-beta1, 2, and 3 mRNA and TGF-beta1 and 2 protein levels at 800, 1,000, and 1,200 mJ/cm2 for 24 hours and 48 hours. RESULTS: TGF-beta1 mRNA levels were increased at both 24 hr and 48 hr, TGF-beta2 mRNA levels were decreased at both 24 hr and 48 hr, and TGF-beta3 mRNA levels were increased at 24 hr and similar to control at 48 hr. TGF-beta1 protein levels were increased at 48 hr but decreased at 24 hr. TGF-beta2 protein levels were decreased at both 24 hr and 48 hr. CONCLUSION: The results suggest a possible role for TGF-beta1 after NBUVB irradiation and opposing roles for TGF-beta1 and TGF-beta2 isoforms in NBUVB irradiation.
Apoptosis ; Enzyme Multiplied Immunoassay Technique ; Epidermis ; Humans ; Keratinocytes ; Protein Isoforms ; RNA, Messenger ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

BACKGROUND: Although it is well known that transforming growth factor beta (TGF-beta) may induce catagen change of hair follicles and inhibit hair growth, it is still unclear which subtype of TGF-beta and its specified receptor might be expressed in human hair follicles of androgenetic alopecia (AGA) patients. OBJECTIVE: To delineate precise expression of TGF-beta subtype in human hair follicles of androgenetic alopecia patients. METHODS: Immunohistochemical studies were performed on paraffin sections of human hair follicles by applying type 1, 2, and 3 TGF-beta antibodies and type I and II receptor antibodies. We ascertained the expression of TGF-beta subtype in hair follicles of androgenetic alopecia patients. We also compared the expression pattern of each type of TGF-beta receptor. We evaluated the change of TGF-beta expression of hair follicles in the catagen phase. RESULTS: TGF-beta1 was well-expressed in the outer area of the inner root sheath (IRS) or dermal connective sheath area. TGF-beta2 was commonly expressed in the inner 1/2 of the outer root sheath (ORS). TGF-beta3 was expressed in the hair cortex, IRS, and cuticle in normal hair follicles obtained from both the vertex and occipital area. On the contrary, in specimens from AGA, the enhanced expression of type 2 TGF-beta or type II receptor was observed in the vertex area (bald) compared to the occipital area (non bald). When the expression patterns of TGF-beta 1, 2, and 3 were compared between anagen and catagen phases, TGF-beta2 and 3 were positively expressed in the epithelial strands and secondary hair germs in the catagen phase. The immunoreactivities of TGF-beta 1 and 2 were intensified in the ORS areas of the catagen phase. CONCLUSION: The expression of type 1, 2 TGF-beta and type I and II receptors in follicular epithelial cells might be related to catagen induction and development of androgenetic alopecia of human hair in vivo.
Alopecia ; Antibodies ; Epithelial Cells ; Hair Follicle* ; Hair* ; Humans* ; Paraffin ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3

OBJECTIVETo investigate the effects of exogenous TGF-β3 on the expression of endogenous TGF-b3 in hepatic stellate cell (HSC).

METHODSHSCs were cultured and divided into two groups: TGF-β3 group and blank control group, the cells of TGF-β3 group were exposed to TGF-b3 (10 ng/ml), whereas the blank control group was not treated. The cells were incubated in the presence of exogenous TGF-β3 and then (1) were harvested at 0h, 1h, 2h, 4h, 12h, 24h, and real time PCR was performed to detect the mRNA expression of endogenous TGF-β3. (2) The cells were collected at 0h, 1h, 6h, 12h, and western-blot was used to detect the protein synthesis of endogenous TGF-β3 in HSC; (3) The cell culture supernatant was harvested at 0h, 1h, 2h, 4h, 8h, 14h, 24h, and ELISA was performed to measure the total protein of extracellular TGF-β3; HSCs were treated with TGF-β3 (10 ng/ml) for 2h. The cells were then incubated in serum-free medium and the cell culture supernatant was harvested at 2.25h, 2.5h, 3h, 4h, 6h, 10h and 14h. ELISA was used to detect the extracellular secret ion of endogenous TGF-β3 by HSCs.

RESULTS(1) Exogenous TGF-β3 treatment induced a marked increase in TGF-β3 mRNA expression. By 2h of exogenous TGF-β3 treatment, maximal TGF-β3 mRNA expression levels (2.796 ± 0.518) of 2.74 fold above control values (1.022 ± 0.038) was reached (P < 0.05). Thereafter, TGF-β3 mRNA expression level declined, and the expression level was maintained at level of 1.45-fold for at least 10h and was 1.18-fold above control values by 24h TGF-β3 treatment (P < 0.05); (2) No significant difference about the intracellular protein expression level of endogenous TGF-β3 was found between two groups. (P > 0.05); (3) The total expression level of TGF-β3 reached a peak [(18.931 ± 2.904) ng/ml] at 4h after TGF-β3 treatment (1.89-fold higher than basic TGF-β3 (10 ng/ml). After that, it slowly declined. The expression peak [(0.835 ± 0.027) ng/ml] induction of extracellular secreted TGF-β3 was at 3h (32.12-fold higher than control [(0.026 ± 0.022) ng/ml], (P < 0.05). Thereafter, TGF-β3 slowly decreased after the peak time, and their expressions were still statistically significant as compared to the control (P < 0.05).

CONCLUSIONExogenous TGF-β3 could increase the expression of endogenous TGF-β3 mRNA and extracellular secreted TGF-β3 protein obviously.

OBJECTIVE: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease. METHODS: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant. RESULTS: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue. CONCLUSION The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.
Cartilage Oligomeric Matrix Protein/genetics* ; Chondromatosis, Synovial ; Humans ; Synovial Membrane ; Temporomandibular Joint ; Transforming Growth Factor beta3

PURPOSE: Transforming growth factor (TGF)-beta is recognized as being associated with cataractogenesis. We quantitated the mRNA expression of TGF-beta isoforms in cataractous crystalline lens to determine the effect of the isoforms on cataractogenesis. METHODS: With lens epithelial cells from thirty eyes in thirty patients, the mRNA expressions of TGF-beta1, beta2 and beta3 were quantitated by real-time SYBR Green polymerase chain reaction and the results were compared according to cataract type and presence of diabetes mellitus. RESULTS: Each isoform mRNA of TGF-beta was expressed: TGF-beta3 in all 30 eyes, TGF-beta1 in 29 eyes (96.7%), with the exception being one diabetic senile cataract, and TGF-beta2 in 9 eyes. The amount of TGF-beta1 mRNA expression was significantly lower in the diabetic cataracts than in the non-diabetic cataracts (P=0.056). CONCLUSIONS: TGF-beta was associated with cataractogenesis. It is significant that the expression of TGF-beta2 mRNA was decreased in all cataracts. The decrease of TGF-beta1 mRNA expression was more meaningful in the diabetic cataracts than in the non-diabetic cataracts.
Cataract* ; Diabetes Mellitus ; Epithelial Cells* ; Humans ; Lens, Crystalline ; Polymerase Chain Reaction ; Protein Isoforms ; RNA, Messenger* ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3 ; Transforming Growth Factors

PURPOSE: We expected that benign and malignant cartilagenous tumors may be distinguished, and that the growth factors may be correlated with oncologic outcomes according to their expression of growth factors. MATERIALS AND METHODS: Immunohistochemical study of some growth factors (bFGF, IGF, TGF-beta1, TGF-beta3) were performed upon paraffin-embedded tissues of 11 enchondroma and 25 chondrosarcoma patients who were treated surgically in our hospital. The Envision+system was used to performed the immunohistochemistry. RESULTS: bFGF was more highly expressed in the enchondroma group (p=0.04), and IGF-I was expressed more so in grade 3 chondrosarcoma than the other grades (p=0.012). The co-expressions of IGF-I and TGF-beta3 were remarkable in the chondrosarcoma group (p<0.001). Four metastases developed among the eleven patients of the TGF-beta3 expression group, and TGF-beta3 expression was found to correlate with distant metastasis in chondrosarcoma (p=0.026). Differences in recurrences or metastases according to the surgical margin between factor-expression group and factor-non-expression group were not significant in all growth factors. CONCLUSION: In chondrosarcoma, TGF-beta3 is closely related to metastasis. In addition, bFGF and IGF-I may be a guideline for the differentiation of benign and malignant cartilagenous tumors and of help when deciding the treatment plan.
Chondroma ; Chondrosarcoma* ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Neoplasm Metastasis* ; Recurrence ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta3

BACKGROUND: Because of the clinical and histological similarities of keratoacanthoma(KA) and squamous cell carcinoma(SCC), it is often difficult to differentiate. Transforming growth factor-betas (TGF-betas) are the multifunctional peptides that regulate the cellular growth and differentiation. It has been known that the isoforms of TGF-beta(TGF-beta1, TGF-beta2, TGF-beta3) are differently expressed in human cancers such as basal cell carcinoma, pancreatic cancer, thyroid cancer, etc. OBJECTIVE: The purpose of this study was to examine the expression patterns of TGF-beta isoforms on KA and SCC using the immunohistochemical staining method with anti-TGF-betas antibodies and to evaluate the usefulness of this method in distinguishing each other. METHODS: We performed immunoperoxidase staining(LSAB technique) using polyclonal anti-TGF-beta1, b2, and b3 antibodies from the formalin-fixed, paraffin-embedded biopsy specimens obtained from 11 patients with KA, 11 pntients with SCC, and 10 healthy volunteers. RESULTS: In the normal skins, TGF-beta1, b2 and b3 were almost negative or only weakly positive in the epidermis, whereas TGF-beta3 was moderately to strongly positive in the suprabasal layer. In KAs, the expression patterns of TGF-beta1, b2, and b3 were similar to those of the normal skins. In SCCs, however, the expression of TGF-beta1 was increased and TGF-beta3 was decreased compared with the normal skins. CONCLUSION: In these results, the immunohistochemical staining using the anti-TGF-betas antibodies, especially anti-TGF-beta1 and b3, can be used for the differentiation of KA and SCC. Also, it can be suggested that the charige of expressions of TGF-beta isoforms in the epidermis may play an important role in the carcinogenesis of SCC.
Antibodies ; Biopsy ; Carcinogenesis ; Carcinoma, Basal Cell ; Carcinoma, Squamous Cell* ; Epidermis ; Healthy Volunteers ; Humans ; Keratoacanthoma* ; Pancreatic Neoplasms ; Peptides ; Protein Isoforms ; Skin ; Thyroid Neoplasms ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3

The expression patterns of transforming growth factor-betas (TGF-betas) were studied immunohis-tochemically in hepatic erythropoietic cells and hepatocytes of 3 human fetal livers from 21 to 26 gestation weeks. The results obtained 1. TGF-beta1 was weakly expressed at first in polychromatophilic erythroblast and more strongly in acidophilic erythroblast, but not in reticulocytes and mature red blood cells. The expression of TGF-beta1 was occasionally found in hepatocytes and sinusoidal endothelial cells. 2. TGF-beta2 was most strongly expressed than TGF-beta1 and beta3 in the maturation stages from proerythroblast to polychromatophilic erythroblasts, and weakly in some acidophilic erythroblasts, but not in hepatocytes and 3. TGF-beta3 was weakly expressed in proerythroblast and basophilic erythroblast, and more strongly than TGF-beta1 in hepatocytes with granular pattern. TGF-beta3 was not expressed in sinusoidal endothelium, but weakly in endothelium of portal vein and in connective tissue of portal area. In summary, TGF-beta1, beta2, beta3 demonstrated various patterns of expression in hepatocytes and erythropoietic cells of some maturation stages, but were not expressed in reticulocytes and mature red blood cells. It is suggested that the characteristic expression patterns of TGF-beta1, beta2, beta3 are closely associated with the maturation of hepatic erythropoietic cells and hepatocytes.
Basophils ; Connective Tissue ; Endothelial Cells ; Endothelium ; Erythroblasts ; Erythrocytes ; Erythropoiesis* ; Hepatocytes ; Humans* ; Liver ; Portal Vein ; Pregnancy ; Protein Isoforms* ; Reticulocytes ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3

Pulmonary vascular hypertension is characterized by migration and proliferation of smooth muscle cells accompanying abnormal synthesis and accumulation of extracellular proteins in vascular wall. The aim of this study is to define the role of endogneous TGF-betas and PDGF in the process of remodeling vessels through determining the temporal and spatial distribution of these growth factors in hypertensive pulmonary vessels in monocrotaline-induced pulmonary hypertension in rat. Sprague-Dawley rats were sacrificed 12 hours, 1, 2, 4, 7, 10, 14, 21, 28, and 56 days after treatment. The morphometric analysis of medial thickening and immunohistochemical study using antibodies to TGF-beta1, TGF-beta2, TGF-beta3, and PDGF were performed. Immunoreactivities for TGF-beta1 and TGF-beta3 were increased from the 14th day in the medial smooth muscle cells and PDGF showed increased expression from the 21st day in the medial smooth muscle cells. No difference in TGF-beta2 immunoreactivity was found between control and experimental groups. The expression of TGF-beta1, TGF-beta3 and PDGF increased in medial layers with the progressive thickening of pulmonary arteries which was considered to have close relation to medial hypertrophy of pulmonary arterioles. In the case of PDGF, however, the morphologic change occurred before increase in immunoreactivity was observed in the medial layer of pulmonary arterioles. Moreover, the function of isoforms of TGF-beta has yet to be completely elucidated; the different affinity to receptors and the degree of expression of these receptors that are supposed to affect the function of growth factors. Thus, further studies are needed.
Animals ; Antibodies ; Arterioles ; Hypertension ; Hypertension, Pulmonary* ; Hypertrophy ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Monocrotaline ; Myocytes, Smooth Muscle ; Protein Isoforms ; Pulmonary Artery ; Rats* ; Rats, Sprague-Dawley ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3