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

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

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

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

The development of eye is a very dynamic process in which various cells and tissues from diverse originneuroectoderm, surface ectoderm and mesenchyme, undergo induction, mitosis and differentiation. During this process advances, many growth factors are involved. Transforming growth factor betas (TGF-betas) are the pivotal growth factors during cellular growth, differentiation, matrix formation, migration and wound healing. Especially during the development of tissues, TGF-beta s are secreted and induce growth and differentiation of adjacent cells. To investigate the functions of TGF-betas during the development of eye, we studied the expression of TGF-betas in rat embryos. For this study, Sprague-Dawley rat embryos were taken on the 11th 13th, 15th, 17th and 19th day of gestation. To confirm the morphological changes of eyes on each developmental stage, sections were stained with hematoxylin and eosin. Then, to document the expressive patterns of TGF-beta1, beta2, beta3 and TGF-beta receptor type II (TbetaR), immunohistochemistry was applied. The results were obtained as follows: TGF-beta1 was partially expressed in the lens only on the 19th day of gestation. TGF-beta2 was expressed in the retina and lens on the 11th and 13th day, while it was detected in most areas of the eye from the 15th to 19th day. TGF-beta3 was expressed only in the pigment cell layer of the retina on the 11th day, but it was detected in various areas along the advance of the development. Immunoreactivity of TGF-beta3 was always weaker than TGF-beta2. TbetaR showed strong immunoreactivity in where the reactivity of TGF-beta2 was detected. These results indicate that TGF-beta2 and beta3 play important roles during the development of eye.
Animals ; Cornea ; Ectoderm ; Embryonic Structures ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Mesoderm ; Mitosis ; Pregnancy ; Rats* ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta ; Retina ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3 ; Wound Healing

The roles of TGF-beta1, beta2 and beta3 according to gestational ages and histodifferentiation were studied using immunohistochemistry with rat fetuses. 1. From day 14 to 21 of fetal rat, all the TGF-beta1, beta2 and beta3 were expressed in endocardium, myocardium, bronchiole, tunica intima of blood vessles, mucosa and serosa of intestine, striated muscle, hepatic capsule, hepatic hemopoietic cells, meninges, epidermis and dermis. 2. From day 14 to 21 of fetal rat, TGF-beta1 was not expressed in the smooth muscle of blood vessel and intestinal tract, alveolar cell and renal tubular cell. TGF-beta2 was not expressed in the smooth muscle of blood vessel and intestinal tract and alveolar cell. TGF-beta3 was not expressed in osteocyte, alveolar cell, and basement membrane of renal cuboidal epithelial cell. And TGF-betas expressed especially in early or late gestational age and the degree of expression increased or decreased with gestational age. 3. The TGF-beta1, beta2 and beta3 were expressed in tissues originated from 3 germ layers except several tissues, and those originated from mesoderm exhibited strong expression. The TGF-beta1 was expressed more widely than TGF-beta2 and beta3 during gestation. In summary, TGF-beta1, beta2 and beta3 were considered as important control factors of cell to cell interaction in the morphogenesis of tissues during fetal development.
Animals ; Basement Membrane ; Blood Vessels ; Bronchioles ; Cell Communication ; Dermis ; Endocardium ; Epidermis ; Epithelial Cells ; Fetal Development ; Fetus ; Germ Layers ; Gestational Age ; Immunohistochemistry ; Intestines ; Meninges ; Mesoderm ; Morphogenesis ; Mucous Membrane ; Muscle, Smooth ; Muscle, Striated ; Myocardium ; Osteocytes ; Pregnancy ; Rats* ; Serous Membrane ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3 ; Transforming Growth Factors* ; Tunica Intima

BACKGROUNDNeural stem cells (NSCs) are a self-renewing and multipotent population of the central nervous system (CNS), which are active during development and maintain homeostasis and tissue integrity throughout life. Microglias are an immune cell population resident in the CNS, which have crucial physiological functions in the developing and adult CNS. This study aimed to investigate that whether microglia co-cultured with NSCs could promote astrogliogenesis from NSCs.

METHODSMicroglia and NSCs were co-cultured in 24-well insert plates. NSCs were plated in the bottom of the well and microglia in the insert. Fluorescent staining, Western blotting and RT-PCR were used to determine the effect of microglia on NSCs differentiation.

RESULTSCo-culture of microglia and NSCs promoted astrogliogenesis from NSCs. Several key genes, such as Notch 1, Notch 2, Notch 3, Hes 5, and NRSF were downregulated, while the critical genes Id1 and Id2 were upregulated. BMP2 and FGF2 were upregulated.

CONCLUSIONMicroglias act as a regulator of NSCs astrogliogenesis.

Animals ; Astrocytes ; cytology ; metabolism ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Blotting, Western ; Bone Morphogenetic Protein 2 ; genetics ; Cell Differentiation ; genetics ; physiology ; Cells, Cultured ; Coculture Techniques ; methods ; Fibroblast Growth Factor 2 ; genetics ; Inhibitor of Differentiation Protein 1 ; genetics ; Inhibitor of Differentiation Protein 2 ; genetics ; Microglia ; cytology ; metabolism ; Microscopy, Fluorescence ; Neural Stem Cells ; cytology ; metabolism ; Rats ; Repressor Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effects of transforming growth factor beta(1) (TGF-beta(1)) and bone morphogenetic protein 2 (BMP2) combined with heparin on odontoblast differentiation.

METHODSTrypsin-isolated dental papillae from day 17 mandibular first molar were cultured in semisolid-agar medium for 6d. Recombinant human TGF-beta(1) and BMP2 combined with heparin were added to the medium.

RESULTSTGF-beta(1) and BMP2 combined with heparin induced differentiation of odontoblasts and promoted matrix secretion. Odontoblast differentiation never occurred when TGF-beta(1) or BMP2 were added alone to the medium, whereas an increase in extracellular matrix production was observed.

CONCLUSIONThese results demonstrate that both TGF-beta(1) and BMP2 stimulate the cytological and functional differentiation of preodontoblasts, and that heparin might play important role as a substrate.

Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; pharmacology ; Cell Differentiation ; drug effects ; Heparin ; pharmacology ; Mice ; Odontoblasts ; cytology ; drug effects ; Transforming Growth Factor beta ; pharmacology ; Transforming Growth Factor beta1