Key Specifications Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, M||WB, IHC||Rb||Affinity Purified||Polyclonal Antibody|
|Description||Anti-ATH 5 Antibody|
|Presentation||Affinity purified immunoglobulin. Precipitated antibody in a solution of 50% saturated ammonium sulfate and PBS containing no preservatives.|
|Safety Information according to GHS|
|Material Size||100 µg|
|RABBIT ANTI-ATH 5 (MATH5)||2459030|
|RABBIT ANTI-ATH 5 (MATH5) -2560994||2560994|
|RABBIT ANTI-ATH 5 (MATH5) -2634650||2634650|
|RABBIT ANTI-ATH 5 (MATH5) -2650880||2650880|
|RABBIT ANTI-ATH 5 (MATH5) -2665010||2665010|
|RABBIT ANTI-ATH 5 (MATH5) -2689078||2689078|
|RABBIT ANTI-ATH 5 (MATH5) -2728431||2728431|
|RABBIT ANTI-ATH 5 (MATH5) -2766505||2766505|
|RABBIT ANTI-ATH 5 (MATH5) AFFINITY PURIFIED - 2712412||2712412|
|RABBIT ANTI-ATH 5 (MATH5) AFFINITY PURIFIED POLYCLONAL ANTIBODY - 2008616||2008616|
References | 11 Available | See All References
|Reference overview||Application||Pub Med ID|
|Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences. |
Del Debbio, CB; Peng, X; Xiong, H; Ahmad, I
BMC neuroscience 14 130 2013
The neural stem cells discovered in the adult ciliary epithelium (CE) in higher vertebrates have emerged as an accessible source of retinal progenitors; these cells can self-renew and possess retinal potential. However, recent studies have cast doubt as to whether these cells could generate functional neurons and differentiate along the retinal lineage. Here, we have systematically examined the pan neural and retinal potential of CE stem cells.Molecular and cellular analysis was carried out to examine the plasticity of CE stem cells, obtained from mice expressing green fluorescent protein (GFP) under the influence of the promoter of the rod photoreceptor-specific gene, Nrl, using the neurospheres assay. Differentiation was induced by specific culture conditions and evaluated by both transcripts and protein levels of lineage-specific regulators and markers. Temporal pattern of their levels were examined to determine the expression of genes and proteins underlying the regulatory hierarchy of cells specific differentiation in vitro. Functional attributes of differentiation were examined by the presence of current profiles and pharmacological mobilization of intracellular calcium using whole cell recordings and Fura-based calcium imaging, respectively. We demonstrate that stem cells in adult CE not only have the capacity to generate functional neurons, acquiring the expression of sodium and potassium channels, but also respond to specific cues in culture and preferentially differentiate along the lineages of retinal ganglion cells (RGCs) and rod photoreceptors, the early and late born retinal neurons, respectively. The retinal differentiation of CE stem cells was characterized by the temporal acquisition of the expression of the regulators of RGCs and rod photoreceptors, followed by the display of cell type-specific mature markers and mobilization of intracellular calcium.Our study demonstrates the bonafide retinal potential of adult CE stem cells and suggests that their plasticity could be harnessed for clinical purposes once barriers associated with any lineage conversion, i.e., low efficiency and fidelity is overcome through the identification of conducive culture conditions.
|Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease. |
Moles, A; Tarrats, N; Fernández-Checa, JC; Marí, M
The Journal of biological chemistry 287 1178-88 2012
Niemann-Pick disease (NPD) is a lysosomal storage disease caused by the loss of acid sphingomyelinase (ASMase) that features neurodegeneration and liver disease. Because ASMase-knock-out mice models NPD and our previous findings revealed that ASMase activates cathepsins B/D (CtsB/D), our aim was to investigate the expression and processing of CtsB/D in hepatic stellate cells (HSCs) from ASMase-null mice and their role in liver fibrosis. Surprisingly, HSCs from ASMase-knock-out mice exhibit increased basal level and activity of CtsB as well as its in vitro processing in culture, paralleling the enhanced expression of fibrogenic markers α-smooth muscle actin (α-SMA), TGF-β, and pro-collagen-α1(I) (Col1A1). Moreover, pharmacological inhibition of CtsB blunted the expression of α-SMA and Col1A1 and proliferation of HSCs from ASMase-knock-out mice. Consistent with the enhanced activation of CtsB in HSCs from ASMase-null mice, the in vivo liver fibrosis induced by chronic treatment with CCl(4) increased in ASMase-null compared with wild-type mice, an effect that was reduced upon CtsB inhibition. In addition to liver, the enhanced proteolytic processing of CtsB was also observed in brain and lung of ASMase-knock-out mice, suggesting that the overexpression of CtsB may underlie the phenotype of NPD. Thus, these findings reveal a functional relationship between ASMase and CtsB and that the ablation of ASMase leads to the enhanced processing and activation of CtsB. Therefore, targeting CtsB may be of relevance in the treatment of liver fibrosis in patients with NPD.
|Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis. |
Dixon, LJ; Berk, M; Thapaliya, S; Papouchado, BG; Feldstein, AE
Laboratory investigation; a journal of technical methods and pathology 92 713-23 2012
Non-alcoholic steatohepatitis (NASH) is typically associated with pro-apoptotic caspase activation. A potential role for pro-inflammatory caspases remains incompletely understood. Our aims were to examine a potential role of caspase-1 in the development of liver damage and fibrosis in NASH. C57BL/6 wild type (WT) developed marked steatohepatitis, activation, fibrosis and increased hepatic caspase-1 and interleukin-1β expression when placed on the methionine- and choline-deficient (MCD) diet. Marked caspase-1 activation was detected in the liver of MCD-fed mice. Hepatocyte and non-parenchymal fractionation of the livers further demonstrated that caspase-1 activation after MCD feeding was mainly localized to non-parenchymal cells. Caspase-1-knockout (Casp1(-/-)) mice on the MCD diet showed marked reduction in mRNA expression of genes involved in inflammation and fibrogenesis (tumor necrosis factor-α was 7.6-fold greater in WT vs Casp1(-/-) MCD-fed mice; F4/80 was 1.5-fold greater in WT vs Casp1(-/-) MCD-fed mice; α-smooth muscle actin was 3.2-fold greater in WT vs Casp1(-/-) MCD-fed mice; collagen 1-α was 7.6-fold greater in WT vs Casp1(-/-) MCD-fed mice; transforming growth factor-β was 2.4-fold greater in WT vs Casp1(-/-) MCD-fed mice; cysteine- and glycine-rich protein 2 was 3.2-fold greater in WT vs Casp1(-/-) MCD-fed mice). Furthermore, Sirius red staining for hepatic collagen deposition was significantly reduced in Casp1(-/-) MCD-fed mice compared with WT MCD-fed animals. However, serum alanine aminotransferase levels, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were similar in Casp1(-/-) and WT mice on the MCD diet. Selective Kupffer cell depletion by clodronate injection markedly suppressed MCD-induced caspase-1 activation and protected mice from fibrogenesis and fibrosis associated with this diet. The conclusion of this study is that it uncovers a novel role for caspase-1 in inflammation and fibrosis during NASH development.
|Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway. |
Jin-Xing Du,Ming-Yu Sun,Guang-Li Du,Feng-Hua Li,Cheng Liu,Yong-Ping Mu,Gao-Feng Chen,Ai-Hua Long,Yan-Qin Bian,Jia Liu,Cheng-Hai Liu,Yi-Yang Hu,Lie-Ming Xu,Ping Liu
BMC complementary and alternative medicine 12 2012
Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD.
|Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. |
Li X, Sun H, Lin N, Hou X, Wang J, Zhou B, Xu P, Xiao Z, Chen B, Dai J, Hu Y.
Biomaterials 32 8172-81 2011
Severe damages of uterine endometrium which prevent embryos from implantation and placentation finally often result in infertility or pregnant complications. There is lack of effective treatments due to the limitation of native materials available and complexity of the function and internal environment of uterus. In the present study, a collagen targeting basic fibroblast growth factor (bFGF) delivery system was constructed by a collagen membrane loaded with bFGF fused a collagen-binding domain (CBD) to the N-terminal which limits the diffusion of bFGF from collagen. We tested the bFGF delivery system in rats under the severe uterine damage model (partial rat uterine horn excision/reconstruction), and found this delivery system improved regeneration abilities of uterine endometrium and muscular cells, improved vascularization, as well as better pregnancy outcomes in rats. Therefore, this targeting delivery system may be an effective strategy for uterine tissue regeneration.
|Prostate epithelial Pten/TP53 loss leads to transformation of multipotential progenitors and epithelial to mesenchymal transition. |
Martin, P; Liu, YN; Pierce, R; Abou-Kheir, W; Casey, O; Seng, V; Camacho, D; Simpson, RM; Kelly, K
The American journal of pathology 179 422-35 2011
Loss of PTEN and loss of TP53 are common genetic aberrations occurring in prostate cancer. PTEN and TP53 contribute to the regulation of self-renewal and differentiation in prostate progenitors, presumptive tumor initiating cells for prostate cancer. Here we characterize the transformed phenotypes resulting from deletion of the Pten and TP53 tumor suppressors in prostate epithelium. Using the PB-Cre4(+)Pten(fl/fl)TP53(fl/fl) model of prostate cancer, we describe the histological and metastatic properties of primary tumors, transplanted primary tumor cells, and clonal cell lines established from tumors. Adenocarcinoma was the major primary tumor type that developed, which progressed to lethal sarcomatoid carcinoma at approximately 6 months of age. In addition, basal carcinomas and prostatic urothelial carcinomas were observed. We show that tumor heterogeneity resulted, at least in part, from the transformation of multipotential progenitors. CK8+ luminal epithelial cells were capable of undergoing epithelial to mesenchymal transition in vivo to sarcomatoid carcinomas containing osseous metaplasia. Metastasis rarely was observed from primary tumors, but metastasis to lung and lymph nodes occurred frequently from orthotopic tumors initiated from a biphenotypic clonal cell line. Androgen deprivation influenced the differentiated phenotypes of metastases. These data show that one functional consequence of Pten/TP53 loss in prostate epithelium is lineage plasticity of transformed cells.
|Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. |
Jeansson, M; Gawlik, A; Anderson, G; Li, C; Kerjaschki, D; Henkelman, M; Quaggin, SE
The Journal of clinical investigation 121 2278-89 2011
Angiopoietin-1/Tek signaling is a critical regulator of blood vessel development, with conventional knockout of angiopoietin-1 or Tek in mice being embryonically lethal due to vascular defects. In addition, angiopoietin-1 is thought to be required for the stability of mature vessels. Using a Cre-Lox conditional gene targeting approach, we have studied the role of angiopoietin-1 in embryonic and adult vasculature. We report here that angiopoietin-1 is critical for regulating both the number and diameter of developing vessels but is not required for pericyte recruitment. Cardiac-specific knockout of angiopoietin-1 reproduced the phenotype of the conventional knockout, demonstrating that the early vascular abnormalities arise from flow-dependent defects. Strikingly, deletion in the entire embryo after day E13.5 produced no immediate vascular phenotype. However, when combined with injury or microvascular stress, angiopoietin-1 deficiency resulted in profound organ damage, accelerated angiogenesis, and fibrosis. These findings redefine our understanding of the biological roles of angiopoietin-1: it is dispensable in quiescent vessels but has a powerful ability to modulate the vascular response after injury.Full Text Article
|Dual origin of mesenchymal stem cells contributing to organ growth and repair. |
Feng, J; Mantesso, A; De Bari, C; Nishiyama, A; Sharpe, PT
Proceedings of the National Academy of Sciences of the United States of America 108 6503-8 2011
In many adult tissues, mesenchymal stem cells (MSCs) are closely associated with perivascular niches and coexpress many markers in common with pericytes. The ability of pericytes to act as MSCs, however, remains controversial. By using genetic lineage tracing, we show that some pericytes differentiate into specialized tooth mesenchyme-derived cells--odontoblasts--during tooth growth and in response to damage in vivo. As the pericyte-derived mesenchymal cell contribution to odontoblast differentiation does not account for all cell differentiation, we identify an additional source of cells with MSC-like properties that are stimulated to migrate toward areas of tissue damage and differentiate into odontoblasts. Thus, although pericytes are capable of acting as a source of MSCs and differentiating into cells of mesenchymal origin, they do so alongside other MSCs of a nonpericyte origin. This study identifies a dual origin of MSCs in a single tissue and suggests that the pericyte contribution to MSC-derived mesenchymal cells in any given tissue is variable and possibly dependent on the extent of the vascularity.
|tPA is a potent mitogen for renal interstitial fibroblasts: role of beta1 integrin/focal adhesion kinase signaling. |
Hao, S; Shen, H; Hou, Y; Mars, WM; Liu, Y
The American journal of pathology 177 1164-75 2010
Proliferation and expansion of interstitial fibroblasts are predominant features of progressive chronic kidney diseases. However, how interstitial fibroblast proliferation is controlled remains ambiguous. Here we show that tissue-type plasminogen activator (tPA) is a potent mitogen that promotes interstitial fibroblast proliferation through a cascade of signaling events. In vitro, tPA promoted cell proliferation of rat kidney fibroblasts (NRK-49F), as assessed by cell counting, cell proliferation assay, and bromodeoxyuridine labeling. tPA also accelerated NRK-49F cell cycle progression. Fibroblast proliferation induced by tPA was associated with an increased expression of numerous proliferation-related genes, including c-fos, c-myc, proliferating cell nuclear antigen, and cyclin D1. The mitogenic effect of tPA was independent of its protease activity, but required LDL receptor-related protein 1. Interestingly, inhibition of beta1 integrin signaling prevented tPA-mediated fibroblast proliferation. tPA rapidly induced tyrosine phosphorylation of focal adhesion kinase (FAK), which led to activation of its downstream mitogen-activated protein kinase signaling. Blockade of FAK, but not integrin-linked kinase, abolished the tPA-triggered extracellular signal-regulated protein kinase 1/2 activation, proliferation-related gene induction, and fibroblast proliferation. In vivo, proliferation of interstitial myofibroblasts in tPA null mice was attenuated after obstructive injury, compared with the wild-type controls. These studies illustrate that tPA is a potent mitogen that promotes renal interstitial fibroblast proliferation through LDL receptor-related protein 1-mediated beta1 integrin and FAK signaling.
|A critical analysis of Atoh7 (Math5) mRNA splicing in the developing mouse retina. |
Prasov, L; Brown, NL; Glaser, T
PloS one 5 e12315 2010
The Math5 (Atoh7) gene is transiently expressed during retinogenesis by progenitors exiting mitosis, and is essential for ganglion cell (RGC) development. Math5 contains a single exon, and its 1.7 kb mRNA encodes a 149-aa polypeptide. Mouse Math5 mutants have essentially no RGCs or optic nerves. Given the importance of this gene in retinal development, we thoroughly investigated the possibility of Math5 mRNA splicing by Northern blot, 3'RACE, RNase protection assays, and RT-PCR, using RNAs extracted from embryonic eyes and adult cerebellum, or transcribed in vitro from cDNA clones. Because Math5 mRNA contains an elevated G+C content, we used graded concentrations of betaine, an isostabilizing agent that disrupts secondary structure. Although approximately 10% of cerebellar Math5 RNAs are spliced, truncating the polypeptide, our results show few, if any, spliced Math5 transcripts exist in the developing retina (less than 1%). Rare deleted cDNAs do arise via RT-mediated RNA template switching in vitro, and are selectively amplified during PCR. These data differ starkly from a recent study (Kanadia and Cepko 2010), which concluded that the vast majority of Math5 and other bHLH transcripts are spliced to generate noncoding RNAs. Our findings clarify the architecture of the Math5 gene and its mechanism of action. These results have implications for all members of the bHLH gene family, for any gene that is alternatively spliced, and for the interpretation of all RT-PCR experiments.
|Pigment epithelium-derived factor is an intrinsic antifibrosis factor targeting hepatic stellate cells. |
Ho, TC; Chen, SL; Shih, SC; Wu, JY; Han, WH; Cheng, HC; Yang, SL; Tsao, YP
The American journal of pathology 177 1798-811 2010
The liver is the major site of pigment epithelium-derived factor (PEDF) synthesis. Recent evidence suggests a protective role of PEDF in liver cirrhosis. In the present study, immunohistochemical analyses revealed lower PEDF levels in liver tissues of patients with cirrhosis and in animals with chemically induced liver fibrosis. Delivery of the PEDF gene into liver cells produced local PEDF synthesis and ameliorated liver fibrosis in animals treated with either carbon tetrachloride or thioacetamide. In addition, suppression of peroxisome proliferator-activated receptor gamma expression, as well as nuclear translocation of nuclear factor-kappa B was found in hepatic stellate cells (HSCs) from fibrotic livers, and both changes were reversed by PEDF gene delivery. In culture-activated HSCs, PEDF, through the induction of peroxisome proliferator-activated receptor gamma, reduced the activity of nuclear factor-kappa B and prevented the nuclear localization of JunD. In conclusion, our observations that PEDF levels are reduced during liver cirrhosis and that PEDF gene delivery ameliorates cirrhosis suggest that PEDF is an intrinsic protector against liver cirrhosis. Direct inactivation of HSCs and the induction of apoptosis of activated HSCs may be two of the mechanisms by which PEDF suppresses liver cirrhosis.
|Anti-ATH 5 - Data Sheet|