Hematopoietic development is characterized by the dynamic generation of hematopoietic stem/progenitor cells during embryogenesis, and afterward, the maintaining of hematopoietic homeostasis in adult. Mouse model has been appreciated valuable for dissecting the regulatory mechanisms of hematopoietic development. As an important cytokine playing pivotal and versatile roles in the regulation of hematopoiesis, transforming growth factor-beta (TGF-beta) attracts more and more attention. In particular, gene targeting by homologous recombination provides a key means for systematic evaluation of how TGF-beta signaling is involved in hematopoiesis under physiological conditions. To further illustrate the functions and possible mechanisms of TGF-beta in hematopoietic development, hematopoietic phenotypes of targeted mutations and/or dominant negative transgenes of molecules within the TGF-beta signaling pathway are categorized and discussed in this review.
Animals ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; physiology ; Humans ; Signal Transduction ; physiology ; Transforming Growth Factor beta ; physiology

DNA-Binding Proteins ; chemistry ; genetics ; physiology ; Humans ; Liver Cirrhosis ; pathology ; physiopathology ; Receptors, Transforming Growth Factor beta ; physiology ; Signal Transduction ; physiology ; Smad7 Protein ; Trans-Activators ; chemistry ; genetics ; metabolism ; physiology ; Transcription, Genetic ; physiology ; Transforming Growth Factor beta ; physiology ; Transforming Growth Factor beta1

Apoptosis ; physiology ; Bronchopulmonary Dysplasia ; physiopathology ; Chronic Disease ; Humans ; Infant, Newborn ; Infant, Premature ; Lung ; pathology ; physiopathology ; Receptors, Transforming Growth Factor beta ; physiology ; Transforming Growth Factor beta ; classification ; physiology

OBJECTIVETo examine the expression of activin A (ACT A) and transforming growth factor-beta 1 (TGF-beta 1) during mandibular lengthening and elucidate the difference between the role of ACT A and TGF-beta 1 during mandibular distraction osteogenesis.

METHODSkeletally mature white new zealand rabbits were established right mandibular distraction osteogenesis model. The regenerating tissue of animals' lengthened mandibes were harvested at different time points to have immunohistochemistric research of ACT A, TGF-beta 1 protein and analysis ACT A, TGF-beta 1 mRNA by using RT-PCR semiquantitative mean.

RESULTSAT the end of latency period day, positive stain of ACT A were found in the osteoblasts while positive stain of TGF-beta 1 was found in mesenchymal cells. At the end of distraction phase, fibrosis tissue had no stain of ACT A, but had strong stain of TGF-beta 1. At the period of fixation days of 20 days, both cytoplasm of osteoblasts and extracellular matrix in primary mineralization front were strongly stained of ACT A. The osteoblasts, osteoid and osteocytes in peripheral new bone zone were moderately stained of ACT A. TGF-beta 1 had strongly positive stained in fibrosis zone and weekly positive stained in primary mineralization front and peripheral new bone zone. There were also broad activin A stains in cytoplasm of osteoblasts, osteoid and cytoplasm of ACT A, TGF-beta 1 in osteocytes after distraction for 30 days. Activin A mRNA began to express at the end of latency period. Expression for activin A mRNA increased gradually along with the beginning of distraction and at the peak in distraction of 10 days and 20 days, while TGF beta 1 mRNA increased at the peak at the end of latency period.

CONCLUSIONACT A and TGF beta 1 have different role during rabbit mandibular distraction osteogenesis.

Activins ; analysis ; physiology ; Animals ; Female ; Immunohistochemistry ; Inhibin-beta Subunits ; analysis ; physiology ; Mandible ; surgery ; Osteogenesis, Distraction ; Rabbits ; Transforming Growth Factor beta ; analysis ; physiology ; Transforming Growth Factor beta1

Transforming growth factor-β (TGF-β) members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II (TβR II) and type I (TβRI) and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes (DUBs). In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regulatory roles of these DUBs as a driving force for cancer progression as well as their underlying working mechanisms are also discussed.
Animals ; Humans ; Molecular Targeted Therapy ; Receptors, Transforming Growth Factor beta ; metabolism ; Signal Transduction ; Smad Proteins ; physiology ; Transforming Growth Factor beta ; physiology ; Ubiquitin Thiolesterase ; metabolism ; Ubiquitin-Specific Proteases ; Ubiquitination

After the articular cartilage injury, the metabolic level is increased during the progressive degeneration, the chondrocytes secrete a variety of inflammatory factors, and the original cell phenotype is gradually changed. For a long time, a large number of researchers have done a lot of researches to promote anabolism of chondrocytes and to maintain the stability of chondrocyte phenotype. There are many molecular signaling pathways involved in the process of promoting cartilage repair. This review focuses on the key signaling molecules in articular cartilage repair, such as transforming growth factor-beta and bone morphogenetic protein, and reveals their roles in the process of cartilage injury and repair, so that researchers in related fields can understand the molecular mechanism of cartilage injury and repair widely and deeply. Based on this, they may find promising targets and biological methods for the treatment of cartilage injury.
Bone Morphogenetic Proteins ; physiology ; Cartilage, Articular ; growth & development ; injuries ; Chondrocytes ; physiology ; Humans ; Regeneration ; Signal Transduction ; Transforming Growth Factor beta ; physiology

OBJECTIVETo explore the effects and mechanism of mesangial cell (MC) on proliferation and function of osteoblast in vitro from growth factors.

METHODSOsteoblast cultured in vitro were divided into normal blood serum group and MC group and cultured supernatant fluid by 10% serum culture medium and 20% MC culture medium. MTF was used to checked the proliferation of osteoblast at the end of 24, 48, 72, 120 h; Expression of BGP and OPN were tested 72 h and 144 h after culture; Expression of IGF-alpha and TGF-beta were tested 144 h after culture.

RESULTSThe proliferation of osteoblast in MC group was obviously higher than normal blood serum group in different times (P < 0.05); The level of BGP and OPN of osteoblast was obviously higher than normal blood serum group (11.3%, 16.4%, 55.0% and 39.6%); and the level of IGF-alpha and TGF-beta of osteoblast was obviously higher than normal blood serum group (10.1% and 47.7%).

CONCLUSIONMC can directly act on osteoblast, promote the proliferation and function of osteoblast by promoting secretion of TGF-beta.

Animals ; Cell Proliferation ; Male ; Mesangial Cells ; physiology ; Osteoblasts ; physiology ; Osteopontin ; physiology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; physiology

Humans ; Polymorphism, Genetic ; Pulmonary Fibrosis ; genetics ; physiopathology ; Transforming Growth Factor beta ; genetics ; physiology

Animals ; Humans ; Leptin ; genetics ; physiology ; Liver Cirrhosis ; etiology ; RNA, Messenger ; analysis ; Receptors, Cell Surface ; analysis ; physiology ; Receptors, Leptin ; Transforming Growth Factor beta ; genetics ; Transforming Growth Factor beta1

Asthma ; physiopathology ; Humans ; Inflammation ; etiology ; Matrix Metalloproteinase 9 ; analysis ; physiology ; Neutrophil Activation ; Neutrophils ; physiology ; Transforming Growth Factor beta ; physiology