Faculty Opinions recommendation of Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling.

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

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Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium

10.21236/ada471087 ◽

2006 ◽

Author(s):

Gloria Chepko ◽

Leena Hilakivi-Clarke

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Mammary Epithelium ◽

Fetal Mouse ◽

Cell Niche ◽

Mouse Mammary Epithelium

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Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

Current Hypertension Reviews ◽

10.2174/1573402116999201209203015 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mayank Chaudhary

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Blood Pressure Regulation ◽

Biologically Active ◽

Pressure Regulation ◽

Tissue Remodelling ◽

Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

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Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.84.17.6060 ◽

1987 ◽

Vol 84 (17) ◽

pp. 6060-6064 ◽

Cited By ~ 163

Author(s):

S. J. Gendler ◽

J. M. Burchell ◽

T. Duhig ◽

D. Lamport ◽

R. White ◽

...

Keyword(s):

Mammary Epithelium ◽

Mucin Glycoproteins ◽

Human Mammary Epithelium ◽

Partial Cdna

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Insights into therapeutic targets and biomarkers using integrated multi-‘omics’ approaches for dilated and ischemic cardiomyopathies

Integrative Biology ◽

10.1093/intbio/zyab007 ◽

2021 ◽

Author(s):

Austė Kanapeckaitė ◽

Neringa Burokienė

Keyword(s):

Machine Learning ◽

Single Cell ◽

Learning Algorithm ◽

Expression Profiles ◽

Therapeutic Targets ◽

Development Stage ◽

Biological Data ◽

Specific Gene ◽

Tissue Remodelling ◽

Pharmacological Management

Abstract At present, heart failure (HF) treatment only targets the symptoms based on the left ventricle dysfunction severity; however, the lack of systemic ‘omics’ studies and available biological data to uncover the heterogeneous underlying mechanisms signifies the need to shift the analytical paradigm towards network-centric and data mining approaches. This study, for the first time, aimed to investigate how bulk and single cell RNA-sequencing as well as the proteomics analysis of the human heart tissue can be integrated to uncover HF-specific networks and potential therapeutic targets or biomarkers. We also aimed to address the issue of dealing with a limited number of samples and to show how appropriate statistical models, enrichment with other datasets as well as machine learning-guided analysis can aid in such cases. Furthermore, we elucidated specific gene expression profiles using transcriptomic and mined data from public databases. This was achieved using the two-step machine learning algorithm to predict the likelihood of the therapeutic target or biomarker tractability based on a novel scoring system, which has also been introduced in this study. The described methodology could be very useful for the target or biomarker selection and evaluation during the pre-clinical therapeutics development stage as well as disease progression monitoring. In addition, the present study sheds new light into the complex aetiology of HF, differentiating between subtle changes in dilated cardiomyopathies (DCs) and ischemic cardiomyopathies (ICs) on the single cell, proteome and whole transcriptome level, demonstrating that HF might be dependent on the involvement of not only the cardiomyocytes but also on other cell populations. Identified tissue remodelling and inflammatory processes can be beneficial when selecting targeted pharmacological management for DCs or ICs, respectively.

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Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽

10.1136/gutjnl-2020-323363 ◽

2021 ◽

pp. gutjnl-2020-323363

Author(s):

Ester Pagano ◽

Joshua E Elias ◽

Georg Schneditz ◽

Svetlana Saveljeva ◽

Lorraine M Holland ◽

...

Keyword(s):

Colon Cancer ◽

Tumour Growth ◽

Tumour Microenvironment ◽

Tube Formation ◽

Tissue Remodelling ◽

Colon Cancers ◽

Inflammatory Bowel ◽

Ion Pumping ◽

G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

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Genome wide effects of oleic acid on cultured bovine granulosa cells: evidence for the activation of pathways favoring folliculo-luteal transition

BMC Genomics ◽

10.1186/s12864-021-07817-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Vengala Rao Yenuganti ◽

Dirk Koczan ◽

Jens Vanselow

Keyword(s):

Oleic Acid ◽

Granulosa Cells ◽

System Development ◽

Circulatory System ◽

Bioinformatic Analysis ◽

Negative Energy ◽

Tissue Remodelling ◽

Gonadotropin Secretion ◽

Genome Wide

Abstract Background Metabolic stress, as negative energy balance on one hand or obesity on the other hand can lead to increased levels of free fatty acids in the plasma and follicular fluid of animals and humans. In an earlier study, we showed that increased oleic acid (OA) concentrations affected the function of cultured bovine granulosa cells (GCs). Here, we focus on genome wide effects of increased OA concentrations. Results Our data showed that 413 genes were affected, of which 197 were down- and 216 up-regulated. Specifically, the expression of FSH-regulated functional key genes, CCND2, LHCGR, INHA and CYP19A1 and 17-β-estradiol (E2) production were reduced by OA treatment, whereas the expression of the fatty acid transporter CD36 was increased and the morphology of the cells was changed due to lipid droplet accumulation. Bioinformatic analysis revealed that associated pathways of the putative upstream regulators “FSH” and “Cg (choriogonadotropin)” were inhibited and activated, respectively. Down-regulated genes are over-represented in GO terms “reproductive structure/system development”, “ovulation cycle process”, and “(positive) regulation of gonadotropin secretion”, whereas up-regulated genes are involved in “circulatory system development”, “vasculature development”, “angiogenesis” or “extracellular matrix/structure organization”. Conclusions From these data we conclude that besides inhibiting GC functionality, increased OA levels seemingly promote angiogenesis and tissue remodelling, thus suggestively initiating a premature fulliculo-luteal transition. In vivo this may lead to impeded folliculogenesis and ovulation, and cause sub-fertility.

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