Disease relevance of Smad1

• Recently, we showed that the overexpression of type IV collagen (Col IV), a major component of mesangial extracellular matrix, is transcriptionally regulated by Smad1 in diabetic glomerulosclerosis [1].
• These data suggest that the activation of STAT3 and Smad1 participates in the developing process of glomerulosclerosis in experimental glomerulonephritis [1].
• In this study, we investigated the regulation of Smad proteins in the glomeruli of rats with anti-thymocyte serum nephritis [2].
• However, changes in the Smad proteins during the progression of kidney disease are unclear [2].
• We examined whether alphaT treatment induces prevention of renal insufficiency and fibrosis, and affects the TGF-beta/Smad signaling pathway in rats with chronic progressive anti-thymocyte serum (ATS) nephritis induced by repeated ATS injections on days 0 and 7 [3].

High impact information on Smad1

• Treatment with TGF-beta1 also induced a pronounced increase in downstream Smad1 phosphorylation [4].
• We report here the cloning and functional studies of a novel mammalian Mad molecule, Mad3, as well as a rat Mad1 homologue [5].
• Activation of BMP4 pathway in endothelial cells was confirmed by both the up-regulation of Msx genes correlated with apoptosis and the translocation of Smad1 into the nucleus [6].
• In vivo, Id1 expression and Smad1 phosphorylation were co-induced during fibrogenesis [7].
• BDNF actions were shown to depend on activation of ERK1/2 and to converge on the SMAD signaling cascade, possibly after stimulation of TGFbeta2 synthesis/secretion [8].

Chemical compound and disease context of Smad1

• In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-beta/Smad signaling pathway system in carbon tetrachloride (CCl(4))-induced rat experimental liver fibrosis were examined [9].
• This novel finding suggests that Smad activation could be involved in the profibrogenic effects of Ang II in vascular diseases [10].

Biological context of Smad1

• In cerebellar cultures prepared at P6 or P10, BMP4 activates Smad1 signaling to modulate cell differentiation [11].
• Using internal deletions of the promoter, we defined a region between -2,841 to -1,941, which includes the NIS upstream enhancer (NUE), as responsible for the TGF-beta/Smad inhibitory effect [12].
• A variety of Smad chimera constructs were generated and used in transient transfection studies to address this question [13].
• Our findings show a colocalization of the pathway-restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF-beta superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation [14].
• Although the Smad family proteins are critical components of the TGF-beta signaling pathways, the roles of Smad3 in the expression of osteoblastic phenotypes remain poorly understood [15].

Anatomical context of Smad1

• Expression and localization of Smad1, Smad2 and Smad4 proteins in rat testis during postnatal development [16].
• For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation [14].
• Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques [14].
• BMP antagonist Noggin blocked the elevation of phosphorylated Smad1 and the expression of Hes1 as well as reducing the percentage of astrocytic SVZ progenitor cells [17].
• We tested the effects of the ectopic expression of inhibitory Smads in cultured rat smooth muscle cells (SMC) to identify the role of TGF-beta/Smad signaling on the phenotypic modulation of SMC [18].

Associations of Smad1 with chemical compounds

• We have examined the immunohistochemical expression of different Smad molecules in the epithelium of rat ventral prostate before and after castration, in androgen-sensitive Dunning R3327 PAP prostatic tumor cells from untreated and castrated rats, and after treatment with estrogen [19].
• Activin receptor and Smad proteins were present in oocytes at all stages of follicular development; granulosa cells of primary-antral follicles, and theca cells. beta glycan protein was present in oocytes, granulosa cells, and theca cells at all stages of folliculogenesis [20].
• Inhibition of Smads by a dominant-negative mutant Smad4 in the DFMO-treated cells prevented the increased Smad transcription activation [21].
• Nuclear factor (NF)-kappaB, Smad proteins, and the steroid hormone family peroxisome proliferator-activated receptors (PPARs) are involved in regulation of gene transcription during the disease process [22].
• Sphingosine 1-phosphate cross-activates the Smad signaling cascade and mimics transforming growth factor-beta-induced cell responses [23].

Regulatory relationships of Smad1

• The expression of BMP2/4 subsequently increased the phosphorylation of downstream effector Smad1 and the expression of notch signal pathway-induced protein Hes1 in cultured SVZ neurospheres [17].
• Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway [24].
• We demonstrate that both TGFbeta and bone morphogenetic protein (BMP) can induce endogenous Smad1 phosphorylation in intestinal epithelial cells (IECs) [25].

Other interactions of Smad1

• These findings in vivo and in culture suggest that BMP4 and Smad1 signaling participate in regulating postnatal cerebellar differentiation [11].
• RESULTS: Smad1, Smad2 and Smad4 were present throughout testicular development [16].
• The immunostaining of Smad1 and Smad2 were present in spermatogenic cells [16].
• Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal differentiation of cerebellar cells [11].
• Together, these experiments demonstrate that NO by induction of the Smad signaling pathway modulates TIMP-1 expression [26].

Analytical, diagnostic and therapeutic context of Smad1

• Immunohistochemistry and Western blots showed that Smad1 and BMP4 proteins are present in the cerebellum, and that their expression also changes postnatally [11].
• Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration [19].
• The expression of activin/BMP receptor, Smad, and beta glycan mRNAs by postnatal rat ovaries were investigated by real-time PCR [20].
• Smad family proteins have been identified as signal transducers for the TGF-beta superfamily [27].
• To understand the physiological roles of these Smad expressions in the kidney, we first identified the sites of Smad6 and Smad7 expression in the rat kidney by in situ hybridization [28].

References