scholarly journals Gp130-dependent signaling in the podocyte

2014 ◽  
Vol 307 (3) ◽  
pp. F346-F355 ◽  
Author(s):  
Yoshikuni Nagayama ◽  
Gerald S. Braun ◽  
Christina M. Jakobs ◽  
Yuichi Maruta ◽  
Claudia R. van Roeyen ◽  
...  
Keyword(s):  
Renal Function ◽  
Receptor Subunit ◽  
Critical Component ◽  
Glomerular Diseases ◽  
Downstream Signaling ◽  
Stat3 Phosphorylation ◽  
The Common ◽  
Common Signal ◽  
Injury Models

Renal inflammation, in particular glomerular, is often characterized by increased IL-6 levels. The in vivo relevance of IL-6 signaling in glomerular podocytes, which play central roles in most glomerular diseases, is unknown. Here, we show that in normal mice, podocytes express gp130, the common signal-transducing receptor subunit of the IL-6 family of cytokines. Following systemic IL-6 or LPS injection in mice, podocyte IL-6 signaling was evidenced by downstream STAT3 phosphorylation. Next, we generated mice deficient for gp130 in podocytes. Expectedly, these mice exhibited abrogated IL-6 downstream signaling in podocytes. At the age of 40 wk, they did not show spontaneous renal pathology or abnormal renal function. The mice were then challenged using two LPS injury models as well as nephrotoxic serum to induce crescentic nephritis. Under all conditions, circulating IL-6 levels increased markedly and the mice developed the pathological hallmarks of the corresponding injury models such as proteinuria and development of glomerular crescents, respectively. However, despite the capacity of normal podocytes to transduce IL-6 family signals downstream, there were no significant differences between mice bearing the podocyte-specific gp130 deletion and their control littermates in any of these models. In conclusion, under the different conditions tested, gp130 signaling was not a critical component of the (patho-)biology of the podocyte in vivo.

scholarly journals Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects

1998 ◽  
Vol 188 (10) ◽  
pp. 1955-1965 ◽  
Author(s):  
Ulrich A.K. Betz ◽  
Wilhelm Bloch ◽  
Maries van den Broek ◽  
Kanji Yoshida ◽  
Tetsuya Taga ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Ciliary Neurotrophic Factor ◽  
Oncostatin M ◽  
Receptor Subunit ◽  
Signal Transducer ◽  
Conditional Mutant ◽  
The Common ◽  
Common Signal

The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are not viable. To assess the collective role of this cytokine family, we inducibly inactivated gp130 via Cre-loxP–mediated recombination in vivo. Such conditional mutant mice exhibited neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects, demonstrating the widespread importance of gp130-dependent cytokines.

The specification of sympathetic neurotransmitter phenotype depends on gp130 cytokine receptor signaling

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4791-4801
Author(s):  
M. Geissen ◽  
S. Heller ◽  
D. Pennica ◽  
U. Ernsberger ◽  
H. Rohrer
Keyword(s):  
Sympathetic Neurons ◽  
Physiological Role ◽  
Cholinergic Neurons ◽  
Retroviral Vectors ◽  
Sympathetic Ganglia ◽  
The Common ◽  
Common Signal

Sympathetic ganglia are composed of noradrenergic and cholinergic neurons. The differentiation of cholinergic sympathetic neurons is characterized by the expression of choline acetyltransferase (ChAT) and vasoactive intestinal peptide (VIP), induced in vitro by a subfamily of cytokines, including LIF, CNTF, GPA, OSM and cardiotrophin-1 (CT-1). To interfere with the function of these neuropoietic cytokines in vivo, antisense RNA for gp130, the common signal-transducing receptor subunit for neuropoietic cytokines, was expressed in chick sympathetic neurons, using retroviral vectors. A strong reduction in the number of VIP-expressing cells, but not of cells expressing ChAT or the adrenergic marker tyrosine hydroxylase (TH), was observed. These results reveal a physiological role of neuropoietic cytokines for the control of VIP expression during the development of cholinergic sympathetic neurons.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

scholarly journals Stu2p binds tubulin and undergoes an open-to-closed conformational change

2006 ◽  
Vol 172 (7) ◽  
pp. 1009-1022 ◽  
Author(s):  
Jawdat Al-Bassam ◽  
Mark van Breugel ◽  
Stephen C. Harrison ◽  
Anthony Hyman
Keyword(s):  
Conformational Change ◽  
Conformational Transition ◽  
Budding Yeast ◽  
Microtubule Dynamics ◽  
Open Structure ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Common

Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of microtubule-associated proteins (MAPs). The common feature of proteins in this family is the presence of HEAT repeat–containing TOG domains near the NH2 terminus. We have investigated the functions of the two TOG domains of Stu2p in vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics through two separate activities. First, Stu2p binds to a single free tubulin heterodimer through its first TOG domain. A large conformational transition in homodimeric Stu2p from an open structure to a closed one accompanies the capture of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate directly with microtubule ends, at least in part, through its second TOG domain. These two properties lead to the stabilization of microtubules in vivo, perhaps by the loading of tubulin dimers at microtubule ends. We suggest that this mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215 family of MAPs.

scholarly journals Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain

2021 ◽  
Vol 22 (15) ◽  
pp. 7918
Author(s):  
Jisun Hwang ◽  
Bohee Jang ◽  
Ayoung Kim ◽  
Yejin Lee ◽  
Joonha Lee ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Growth Factor Receptor ◽  
Cytoplasmic Domain ◽  
Nih3t3 Cells ◽  
C Elegans ◽  
Downstream Signaling ◽  
Downstream Effectors ◽  
Signaling Events

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.

scholarly journals Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

2021 ◽  
Author(s):  
G. Amato ◽  
T. Saleh ◽  
G. Carpino ◽  
E. Gaudio ◽  
D. Alvaro ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Cell Delivery ◽  
Effective Strategies ◽  
Multiple Strategies ◽  
End Stage ◽  
Therapy Strategies ◽  
Injury Models ◽  
Experimental Liver

Abstract Purpose of Review To describe experimental liver injury models used in regenerative medicine, cell therapy strategies to repopulate damaged livers and the efficacy of liver bioengineering. Recent Findings Several animal models have been developed to study different liver conditions. Multiple strategies and modified protocols of cell delivery have been also reported. Furthermore, using bioengineered liver scaffolds has shown promising results that could help in generating a highly functional cell delivery system and/or a whole transplantable liver. Summary To optimize the most effective strategies for liver cell therapy, further studies are required to compare among the performed strategies in the literature and/or innovate a novel modifying technique to overcome the potential limitations. Coating of cells with polymers, decellularized scaffolds, or microbeads could be the most appropriate solution to improve cellular efficacy. Besides, overcoming the problems of liver bioengineering may offer a radical treatment for end-stage liver diseases.

scholarly journals A Wolf in Another Wolf’s Clothing: Post-Genomic Regulation Dictates Venom Profiles of Medically-Important Cryptic Kraits in India

Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 69 ◽  
Author(s):  
Kartik Sunagar ◽  
Suyog Khochare ◽  
R. R. Senji Laxme ◽  
Saurabh Attarde ◽  
Paulomi Dam ◽  
...  
Keyword(s):  
Negative Impact ◽  
Indian Subcontinent ◽  
Clinical Effectiveness ◽  
Venom Gland ◽  
Western India ◽  
The Common ◽  
Genomic Regulation

The Common Krait (Bungarus caeruleus) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other Bungarus species, commercial Indian antivenoms are only manufactured against B. caeruleus. It is, therefore, imperative to understand the distribution of genetically distinct lineages of kraits, the compositional differences in their venoms, and the consequent impact of venom variation on the (pre)clinical effectiveness of antivenom therapy. To address this knowledge gap, we conducted phylogenetic and comparative venomics investigations of kraits in Southern and Western India. Phylogenetic reconstructions using mitochondrial markers revealed a new species of krait, Romulus’ krait (Bungarus romulusi sp. nov.), in Southern India. Additionally, we found that kraits with 17 mid-body dorsal scale rows in Western India do not represent a subspecies of the Sind Krait (B. sindanus walli) as previously believed, but are genetically very similar to B. sindanus in Pakistan. Furthermore, venom proteomics and comparative transcriptomics revealed completely contrasting venom profiles. While the venom gland transcriptomes of all three species were highly similar, venom proteomes and toxicity profiles differed significantly, suggesting the prominent role of post-genomic regulatory mechanisms in shaping the venoms of these cryptic kraits. In vitro venom recognition and in vivo neutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom of B. caeruleus was neutralised as per the manufacturer’s claim, performance against the venoms of B. sindanus and B. romulusi was poor, highlighting the need for regionally-effective antivenoms in India.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

Sign in / Sign up

Export Citation Format

Share Document