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Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Bone morphogenetic proteins (Bmps) are members of the TGF-beta superfamily of secreted signaling molecules and, together with FGFs, have many morphogenetic roles in the developing embryo. Bmp2 and Bmp4 are strongly expressed in the cardiac mesoderm. FGFs are also expressed before and during hepatic induction, and while liver gene induction occurs normally in the ventral foregut endoderm of Bmp4-homozygous mutant embryos, the initial induction of hepatic genes is inhibited in ventral foregut expiants that are treated with a Bmp inhibitor, noggin. Adding Bmp2 or Bmp4 back to the noggin-inhibited expiants restores hepatic gene induction. These data suggest Bmp signaling is both redundant as well as important for liver induction, possibly through enhancing the hepatic competence of the endoderm.23–25
Embryology of the Female Urogenital System and Clinical Applications
Published in Linda Cardozo, Staskin David, Textbook of Female Urology and Urogynecology - Two-Volume Set, 2017
through the use of trAnsgenic mice cApAble of lAbeling specific cell populAtions At specific time points. using A murine model of fetAl exposure to All-trAns-retinoic Acid on the ninth dAy of conception, sAsAki et Al. [5] demonstrAted thAt All fetAl survivors hAd A short tAil And imperforAte Anus. In femAles, this wAs mAnifest As A common cloAcA in which the urethrA, vAginA, And rectum merged. The process of normAl cloAcAl differentiAtion is under the control of the sonic hedgehog (shh) signAling pAthwAy (Figure 22.3A) [6]. shh immunoreActivity wAs prominent in the rectAl, urethrAl, And blAdder epithelium in normAl mice, but wAs Absent in those with AnorectAl mAlformAtions (ArM). bone morphogenetic protein type 4 (bMP4) immunoreActivity wAs noted in the mesenchyme below the epithelium stAining for shh expression in normAl mice, but wAs Absent in the populAtion with ArM. In A second model using A knockout mouse model for shh, sukegAwA et Al.
Polymer-Based Protein Delivery Systems for Loco-Regional Administration
Published in Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi, Green Synthesis in Nanomedicine and Human Health, 2021
Muhammad Haji Mansor, Emmanuel Garcion, Bathabile Ramalapa, Nela Buchtova, Clement Toullec, Marique Aucamp, Jean Le Bideau, François Hindré, Admire Dube, Carmen Alvarez-Lorenzo, Moreno Galleni, Christine Jérôme, Frank Boury
In the field of cancer treatment, it has been shown that a synergic effect with ionizing radiation could occur upon exposure to BMPs. HrBMP4, for instance, is expressed in the embryonic cortex, indicating its role in the formation of mesoderm and neurogenesis, e.g. morphological differentiation of neural stem cells (Moon et al. 2009; Vescovi et al., 2006). A recent clinical trial carried out on the brain tumour glioblastoma (GBM) is in course after resection or biopsy of the tumour, using convection enhanced delivery (CED) allowing increasing amounts of HrBMP4 solutions combined with Gd-DTPA and determining the extent of intra-tumour and interstitial drug delivery (DiMeco et al., 2016). HrBMP4 can indeed inhibit the proliferation of brain tumour stem cells, induce their morphological changes to a more differentiated phenotype and reduce their invasiveness (Liu et al., 2016; Piccirillo et al., 2006). The possibility to abolish the tumour’s self-renewal potential by depleting the tumour stem cell compartment with a differentiating, non-toxic compound such as BMP4 is attractive because it could be used to render the stem cells more vulnerable to conventional post-surgery therapies. The differentiated cancer stem cells then could be better eliminated by external beam radiation or internal radiotherapy after loco-regional implantation (Bao et al., 2006). This is well illustrated by Stupp et al. (2007) differentiating strategy: GBM is a heterogeneous tumour that can be initiated and maintained by a minority of CD133+ cancer stem-like cells that have a high tumorigenic potential and a low proliferation rate. Exposure to BMPs can force these CD133+ tumour cells into a more differentiated phenotype characteristic of the CD133 tumour bulk, abolishing their self-renewal potential and increasing their sensitivity to radiotherapy (Stupp et al., 2007). Hence, BMP originally influences multiple signalling pathways originally involved in organogenesis and lineage-specific differentiation but also in cancer stem-like cell maintenance.
Association of growth performance and body conformational traits with BMP4 gene variation in Barki lambs
Published in Growth Factors, 2019
Bone morphogenetic protein 4 (BMP4) is a BMP family member. This protein has anabolic and pleiotropic functions that are assumed to play crucial roles in skeletal development (Hogan 1996); bone formation (Bellusci et al. 1996); and white, beige, and brown adipogenesis regulation (Elsen et al. 2014). During embryonic development, BMP4 is involved in many important processes, such as mesoderm progenitor and endothelial induction, mesodermal differentiation, somite formation, ectodermal differentiation, and myogenesis induction (Graff 1997; Vainio et al. 1993; Graham et al. 1994). Furthermore, BMP4 plays a critical role in metabolism through repressing or promoting oxidative metabolism in cells (Modica and Wolfrum 2017). Many studies have revealed a positive correlation of metabolic rate with growth rate and body mass in guinea fowl and Japanese quail (Dietz and Drent 1997), growth rate in salmonids (Rosenfeld et al. 2015), growth rate in beef cattle (Ellenberger et al. 1989) and growth and body composition in growing lambs (Zhang et al. 2017).
BMP4 circulating levels and promoter (rs17563) polymorphism in risk prediction of idiopathic male infertility
Published in British Journal of Biomedical Science, 2019
F Eslaminejad, F Mashayekhi, MA Osalou, ST Sasani, Z Salehi
Genotyping of BMP4 T152C (rs17563) was determined by PCR-RFLP method using Hph1 restriction enzyme and the following primers: forward 5ʹ- TTCACCATTCATTGCCCAACC-3ʹ and reverse 5ʹ-GAAGCCCCTTTCCCAATCAGG-3ʹ which have been designed by Oligo-primer analysis software (Version 7.54, Molecular Biology Insights, USA). BMP4 serum levels have been measured using Human BMP4 ELISA Kit (ab99982) (Abcam, Cambridge, UK) and antiserum against human BMP4 (n = 35 for each groups). The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The relationship was regarded as significant when they reached p < 0.05. Statistical Package for the Social Sciences (SPSS) version 20.0 (Chicago, IL, USA) was used for data analysis.
Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?
Published in Expert Opinion on Therapeutic Targets, 2018
BMP proteins belong to TGF-β superfamily and their association, particularly BMP-4 and -7, with glaucoma has been widely described. BMP signal transduction is mediated by BMP type 1 and type 2 receptors. Upon ligand binding, BMP type 2 receptor phosphorylates the type 1 receptor, which in turn phosphorylates Smads 1, 5, and 8. Phosphorylated Smads 1/5/8 then interact with Smad 4 and translocate into the nucleus to modulate the transcription of BMP-responsive genes. BMP signaling may also involve noncanonical pathway through MAP kinases [80]. Expression of numerous BMP antagonist proteins, BMP ligands (BMP2, BMP4, BMP5, and BMP7) and BMP receptors (BMPR1a, BMPR1b, and BMPR2), has been detected in human TM cells [81]. One of the studies showed that TM cells secrete BMP-4 and they respond to exogenous BMP-4 via canonical Smad pathway. In this study, BMP-4 was shown to inhibit TGF-β2-induced fibronectin secretion. A BMP antagonist, gremlin, was shown to inhibit BMP-4 activity and hence allow unopposed ECM protein synthesis by TGF-β2 [43]. BMP-7 was shown to inhibit fibrogenesis by preventing TGF-β-induced reduction in matrix breakdown and upregulation of PAI-1. BMP-7-induced inhibition of TGF-β signaling may also involve upregulation of Smad-7, an inhibitory Smad [40]. Hence, TGF-β-mediated effects of Ang-II, at least in part, may involve BMP signaling. It is also of great interest to note that stimulation of proximal tubular cells (HK-2) by Ang-II significantly reduces BMP-7 and this effect was ameliorated by telmisartan, an AT1 receptor blocker [82]. Since AT1 receptor signaling involves both Smad-dependent and -independent pathways, the possibility of crosstalk between AT1 and BMP signaling is likely to exist.