BMP AND smad

Host response to pathogens recruits multiple tissues in part through conserved cell signaling pathways. In C. elegans , the bone morphogenetic protein (BMP) like DBL-1 signaling pathway has a role in the response to infection in addition to other roles in development and post-developmental functions. In the regulation of body size, the DBL-1 pathway acts through cell autonomous signal activation in the epidermis (hypodermis). We have now elucidated the tissues that respond to DBL-1 signaling upon exposure to two bacterial pathogens...

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Throughout development, complex networks of cell signaling pathways drive cellular decision-making across different tissues and contexts. The transforming growth factor β (TGF-β) pathways, including the BMP/Smad pathway, play crucial roles in these cellular responses. However, as the Smad pathway is used reiteratively throughout the life cycle of all animals, its systems-level behavior varies from one context to another, despite the pathway connectivity remaining nearly constant. For instance, some cellular systems require a rapid response, while others require high noise filtering...

Flolistatin-related protein 1 (FSTL1), a secreted glycoprotein that is involved in many physiological functions, has attracted much interest and has been implicated in a wide range of diseases, including heart diseases and inflammatory diseases. In recent years, the involvement of FSTL1 in cancer progression has been implicated and researched. FSTL1 plays a contradictory role in cancer, depending on the cancer type as well as the contents of the tumor microenvironment. As reviewed here, the structure and distribution of FSTL1 are first introduced...

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects...

The use of the FDA-approved osteoinductive growth factor BMP2 is widespread for bone regeneration. However, its clinical application has been hindered by limitations in cell permeability and a short half-life in circulation. To address this issue, we have developed a modified version of BMP2, referred to as Cell Permeable (CP)-BMP2, which possesses improved cell permeability. CP-BMP2 incorporates an advanced macromolecular transduction domain (aMTD) to facilitate transfer across the plasma membrane, a solubilization domain, and recombinant human BMP2...

PURPOSE: TGF-β/BMP signaling pathway plays a significant role in fibrotic cataract. Smurf1, a ubiquitin protein ligase, regulates the TGF-β/BMP signaling pathway through the ubiquitin-proteasome system (UPS). This study aims to investigate the role of Smurf1 in the progression of fibrotic cataract and its underlying mechanism. METHODS: We used a mouse model of injury-induced anterior subcapsular cataract (ASC) and administered the Smurf1 inhibitor A01 for in vivo investigations...

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies such as exencephaly, spina bifida and cleft lip and/or palate. The highly-conserved transcription factor Grainyhead-like 2 (Grhl2) is a critical regulator of tissue fusion, with mouse models lacking Grhl2 function presenting with a fully-penetrant open cranial neural tube (NT), facial and abdominal clefting (abdominoschisis) and an open posterior neuropore. Here we show that Grhl2 interacts with the soluble morphogen-protein and Bone Morphogenetic Protein (BMP) inhibitor Noggin (NOG) to impact tissue fusion during development...

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed...

Transforming growth factor-βs (TGF-βs) and bone morphometric proteins (BMPs) belong to the TGF-β superfamily and perform essential functions during osteoblast and chondrocyte lineage commitment and differentiation, skeletal development, and homeostasis. TGF-βs and BMPs transduce signals through SMAD-dependent and -independent pathways; specifically, they recruit different receptor heterotetramers and R-Smad complexes, resulting in unique biological readouts. BMPs promote osteogenesis, osteoclastogenesis, and chondrogenesis at all differentiation stages, while TGF-βs play different roles in a stage-dependent manner...

The Activin A Receptor type I ALK2 is a critical component of the BMP-SMAD signaling that, in the presence of ligands, phosphorylates cytosolic SMAD1/5/8 and modulates important biological processes, including bone formation and iron metabolism. In hepatocytes, the BMP-SMAD pathway controls the expression of hepcidin , the liver peptide hormone that regulates body iron homeostasis via the BMP receptors ALK2 and ALK3, and the hemochromatosis proteins. The main negative regulator of the pathway in the liver is the transmembrane serine protease 6 (TMPRSS6), which downregulates hepcidin by cleaving the BMP coreceptor hemojuvelin...

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure the adequate supply of iron to the bone marrow for red blood cells production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine FGL1 as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia and in thalassemic mice...

Electrical stimulation (ES) plays an important role in regulating cell osteoblast differentiation. As a noninvasive rehabilitation therapy method, Es has a unique role in postoperative recovery. Bone morphogenetic protein-2 (BMP-2) is the most commonly used bioactive molecule in in situ tissue engineering scaffolds, and it plays an important regulatory role in the whole process of bone injury repair. In this study, the osteogenic regulation of MC-3T3-E1 cells was studied by combining pulsed electrical stimulation (PES) and different concentrations of BMP-2...

Caveolin-1 (CAV1) and Cavin-1 are components of caveolae, both of which interact with and influence the composition and stabilization of caveolae. CAV1 is associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein (BMP) type 2 receptor (BMPR2) is localized in caveolae associated with CAV1 and is commonly mutated in PAH. Here, we show that BMP/Smad signaling is suppressed in pulmonary microvascular endothelial cells of CAV1 knockout mice. Moreover, hypoxia enhances the CAV1/Cavin-1 interaction but attenuates the CAV1/BMPR2 interaction and BMPR2 membrane localization in pulmonary artery endothelial cells (PAECs)...

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores...

INTRODUCTION: This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs). METHODS: Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured...

BACKGROUND: The temporal dynamics of morphogen presentation impacts transcriptional responses and tissue patterning. However, the mechanisms controlling morphogen release are far from clear. We found that inwardly rectifying potassium (Irk) channels regulate endogenous transient increases in intracellular calcium and bone morphogenetic protein (BMP/Dpp) release for Drosophila wing development. Inhibition of Irk channels reduces BMP/Dpp signaling, and ultimately disrupts wing morphology...

BACKGROUND: Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years...

Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of motion segments. Currently, pseudoarthrosis after LIF is an important and unsolved issue, which is closely related to osteobiologies. Of the many signaling pathways, the bone morphogenetic protein (BMP) signaling pathway contributes to osteoblast differentiation, which is generally regulated by SMAD proteins as common in the TGF-β superfamily...

Phosphatidylinositol 4 kinase-β (PI4KB) plays critical roles in human genetic diseases. In zebrafish, Pi4kb is strongly expressed in hair cells (HCs), which are necessary for detecting sound vibrations, head movements, and water motion. However, the role of PI4KB in HC or semicircular canal development is unclear. Herein, we report that pi4kb morphants exhibit insensitivity to sound stimulation and abnormal morphological vestibular organs, including cilium loss in HCs of the cristae and semicircular canal malformation...