Miroslav Blumenberg - Academia.edu (original) (raw)

Papers by Miroslav Blumenberg

A) The genes differentially expressed with a p-value better than 0.01 are marked with da... more A) The genes differentially expressed with a p-value better than 0.01 are marked with dashed line. The table inset shows the numbers of regulated genes used in analysis, selected with a 10−4 cut-off, except for the LPS treatment, where we used 10−3 cut-off because a single study provided statistically less significant values. B) Venn diagrams of overlaps among the selected genes. Note that the more extensive overlaps between the E. coli regulated genes may be due to the larger numbers of such genes, when compared to the list of genes regulated by S. aureus. For studies used in this figure please refer to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0148562#pone.0148562.t001" target="_blank">Table 1</a>.</p

Saudi Journal of Biological Sciences, 2021

Graphical abstract

Journal of Cell Science, 1993

Keratinocytes of the suprabasal compartment of many stratified epithelia synthesize as a major di... more Keratinocytes of the suprabasal compartment of many stratified epithelia synthesize as a major differentiation product a keratin pair, consisting of an acidic and a basic keratin, which accounts for 10–20% of the newly synthesized proteins. While genes of several differentiation-related keratins have been cloned and studied, relatively little is known about the molecular basis underlying their tissue-specific and differentiation-dependent expression. We have chosen to study, as a prototype of these genes, the gene of K3 keratin, which has the unique property of being expressed in the majority of corneal epithelial basal cells but suprabasally in peripheral cornea, the site of corneal epithelial stem cells. Using a monoclonal antibody, AE5, specific for K3 keratin, and a fragment of human K3 gene as probes, we have isolated several cDNA and genomic clones of rabbit K3 keratin. One genomic clone has been sequenced and characterized, and the identity of its coding sequence with that of...

Journal of Bacteriology, 1977

The glutamine synthetase (GS) from Klebsiella aerogenes is similar to that from Escherichia coli ... more The glutamine synthetase (GS) from Klebsiella aerogenes is similar to that from Escherichia coli in several respects: (i) it is repressed by high levels of ammonia in the growth medium; (ii) its biosynthetic activity is greatly reduced by adenylylation; and (iii) adenylylation lowers the pH optimum and alters the response of the enzymes to various inhibitors in the gamma-glutamyl transferase (gammaGT) assay. There are, however, several important differences: (i) the isoactivity point for the adenylylated and non-adenylylated forms in the gammaGT assay occurs at pH 7.55 in K. aerogenes and at pH 7.15 in E. coli; (ii) the non-adenylylated form of the GS from K. aerogenes is stimulated by 60 mM MgCl2 in the gammaGT assay at pH 7.15. A biosynthetic reaction assay that correlates well with number of non-adenylylated enzyme subunits, as determined by the method of Mg2+ inhibition of the gammaGT assay, is described. Finally, we have found that it is necessary to use special methods to harv...

Molecular and Cellular Biology, 1994

Epidermal keratinocytes have important immunologic functions, which is apparent during wound heal... more Epidermal keratinocytes have important immunologic functions, which is apparent during wound healing, in psoriasis, and in allergic and inflammatory reactions. In these processes, keratinocytes not only produce cytokines and growth factors that attract and affect lymphocytes but also respond to the polypeptide factors produced by the lymphocytes. Gamma interferon (IFN-gamma) is one such signaling polypeptide. Its primary molecular effect is activation of specific transcription factors that regulate gene expression in target cells. In this work, we present a molecular mechanism of lymphocyte-keratinocyte signaling in the epidermis. We have induced cutaneous delayed-type hypersensitivity reactions that are associated with an accumulation of lymphocytes. These resulted in activation and nuclear translocation of STAT-91, the IFN-gamma-activated transcription factor, in keratinocytes in vivo and subsequent induction of transcription of keratin K17. Within the promoter of the K17 keratin ...

American Journal of Physiology-Heart and Circulatory Physiology, 2017

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis a... more The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S-adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor...

American journal of human genetics, 1988

Analysis of the cytoskeletal components of early murine embryos has detected expression of two ke... more Analysis of the cytoskeletal components of early murine embryos has detected expression of two keratin proteins, K#8 and K#18, at the 4-8-cell stage. Comparable data for human embryos do not exist, although several processed pseudogenes corresponding to K#8 and K#18 have been discovered in the human genome. Because only genes that are expressed in pre-germ-line and germ-line cells can give rise to processed pseudogenes, the existence of human K#8 and K#18 processed pseudogenes is prima facie evidence for expression of keratins K#8 and K#18 in the early human embryo. We have cloned and determined the complete sequence of a processed pseudogene corresponding to another acidic human keratin. Comparison of its sequence with known sequences of other mammalian keratins indicates that the pseudogene arose from a reverse transcript of a correctly initiated and terminated functional human K#19 gene. This implies expression of K#19 keratin in addition to K#8 and K#18 in the early human embryo...

Acta dermatovenerologica Alpina, Panonica, et Adriatica

Keratin 5 associated restriction fragment length polymorphism in patients with palmoplantar kerat... more Keratin 5 associated restriction fragment length polymorphism in patients with palmoplantar keratoderma of Unna-Thost type re: Acta Dermatovenerol Alp Panon Adriat le: 1992 vu: 1 zv: 4 st: 114-8 rf: 27 dr: svn ab: Hereditary palmoplantar keratodermas of the Unna-Thost type (HPPK-UT) are relatively frequent among the Slovenian and Croatian population. Members of two Slovenian families (33 persons altogether) were investigated for RF1.P (restriction fragment length polymorphism). RFLP of the patients DNA was studied by applying the following endonucleases: Hind III, Taq I, EcoRl, Sac I, BamHI and Msp I. Only digestion with Msp I produced four polymorphic fragments which were identified as a, b, c and d alleles ofkeratin 5.14 out of 15 affected persons expressed the d allele in a heterozygous or homozygous way. In a number of unaffected members the d allele was also present.

Journal of Bacteriology, 1982

The regulatory region of the trp operon of Citrobacter freundii was sequenced and compared with t... more The regulatory region of the trp operon of Citrobacter freundii was sequenced and compared with the corresponding regions of other enteric bacteria. Significant differences were noted in the promoter region. These differences are presumably responsible for the weak expression of the cloned trp operon in Escherichia coli. The presumed operator region, although nonfunctional in E. coli, has dyad symmetry, but the sequence of the symmetrical region differs appreciably from those of operators that can be regulated by the E. coli trp repressor. The sequence of the trp leader region of C. freundii resembles that of other enteric bacteria, suggesting that the C. freundii operon is also regulated by attenuation. Comparison of the sequence of the initial portion of trpE with the homologous regions of E. coli and Salmonella typhimurium indicates that the three organisms probably are evolutionary equidistant.

This article cites 59 articles, 17 of which can be accessed free

Molecular Biology of the Cell, 1990

In the epidermis, retinoids regulate the expression of keratins, the intermediate filament protei... more In the epidermis, retinoids regulate the expression of keratins, the intermediate filament proteins of epithelial cells. We have cloned the 5' regulatory regions of four human epidermal keratin genes, K#5, K#6, K#10, and K#14, and engineered constructs in which these regions drive the expression of the CAT reporter gene. By co-transfecting the constructs into epithelial cells along with the vectors expressing nuclear receptors for retinoic acid (RA) and thyroid hormone, we have demonstrated that the receptors can suppress the promoters of keratin genes. The suppression is ligand dependent; it is evident both in established cell lines and in primary cultures of epithelial cells. The three RA receptors have similar effects on keratin gene transcription. Our data indicate that the nuclear receptors for RA and thyroid hormone regulate keratin synthesis by binding to negative recognition elements in the upstream DNA sequences of the keratin genes. RA thus has a twofold effect on epid...

Human Skin Cancer, Potential Biomarkers and Therapeutic Targets, 2016

Skin cancers constitute arguably the most common and increasingly prevalent human neoplasms. In U... more Skin cancers constitute arguably the most common and increasingly prevalent human neoplasms. In United States alone, it is estimated that 76,400 patients will develop melanoma and 10,100 will die from the disease [1]. Several risk factors, ultraviolet light the most important of these, but also environmental carcinogens, contribute to the increasing incidence of skin cancers, especially among light-skinned individuals [2]. The most common human skin cancers are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but the most serious and most often fatal are malignant melanoma (MM) and Merkel cell carcinoma (MCC) [3]. Basal cell carcinoma is the most common type of skin cancer, caused by ultraviolet (UV) light, specifically UV-B, and its incidence increases with age. Most commonly, it occurs on sunexposed areas, such as the face, neck, scalp, forearms, hands, legs and feet. Usually, it is a slowly growing, very rarely metastasizing, locally destructive tumor, which, if ignored, may invade the underlying tissues, bone or cartilage [4]. Basal cell carcinomas arise in keratinocyte stem cells [5]. Usually, in BCCs, the hedgehog signaling pathway is activated causing neoplastic transformation of keratinocytes. Signaling by smoothened, via the cognate receptors, activates the hedgehog signaling pathway and has been implicated in BCC pathogenesis [6]. The most common treatment for BCC is surgical excision, nowadays using Mohs micrographic surgery to ensure complete excision while sparing the surrounding tissue [4]. Curettage, cryotherapy or laser ablation is sometimes used for lesions considered less risky. Squamous cell carcinoma is the second most common skin cancer worldwide. It usually occurs in sun-exposed areas, frequently on lips, forehead and scalp, ears and pre-auricular regions, but can occur anywhere on skin [7]. It can both invade locally and can metastasize. Chronic sun exposure is the main risk factor for SCC occurrence. Human papillomaviruses and

Textbook of Aging Skin, 2015

Journal of Biological Chemistry, 2000

Epidermal keratinocytes respond to injury by becoming activated, i.e. hyperproliferative, migrato... more Epidermal keratinocytes respond to injury by becoming activated, i.e. hyperproliferative, migratory, and proinflammatory. These processes are regulated by growth factors and cytokines. One of the markers of activated keratinocytes is keratin K6. We used a novel organ culture system to show that tumor necrosis factor ␣ (TNF␣) induces the expression of K6 protein and mRNA in human skin. Multiple isoforms of K6 are encoded by distinct genes and have distinct patterns of expression. By having shown previously that proliferative signals, such as epidermal growth factor (EGF), induce expression of the cytoskeletal protein keratin K6b, we here demonstrate that the same isoform, K6b, is also induced by TNF␣, a proinflammatory cytokine. Specifically, TNF␣ induces the transcription of the K6b gene promoter. By using co-transfection, specific inhibitors, and antisense oligonucleotides, we have identified NFB and C/EBP␤ as the transcription factors that convey the TNF␣ signal. Both transcription factors are necessary for the induction of K6b by TNF␣ and act as a complex, although only C/EBP␤ binds the K6b promoter DNA. By using transfection, site-directed mutagenesis, and footprinting, we have mapped the site that responds to TNF␣, NFB, and C/EBP␤. This site is separate from the one responsive to EGF and AP1. Our results show that the proinflammatory (TNF␣) and the proliferative (EGF) signals in epidermis separately and independently regulate the expression of the same K6b keratin isoform. Thus, the cytoskeletal responses in epidermal cells can be precisely tuned by separate proliferative and inflammatory signals to fit the nature of the injuries that caused them.

Epithelial cell biology, 1992

Among extrinsic modulators of keratinization are certain hormones and vitamins, which makes them ... more Among extrinsic modulators of keratinization are certain hormones and vitamins, which makes them potentially important pharmacological tools for treatment of keratinization disorders. Vitamin D3 and vitamin A, and their metabolites, promote and inhibit keratinization, respectively. We have shown that retinoic acid, via its nuclear receptor, directly suppresses the expression of the keratin genes which are markers of keratinocyte differentiation. Here we present evidence that 1,25(OH)2 vitamin D3 and its nuclear receptor do not directly regulate keratin gene expression. Co-transfection of a vector expressing the nuclear receptor for vitamin D3 with responder DNA constructs containing keratin gene promoters had no effect on the level of activity of keratin gene promoters either in the presence or in the absence of vitamin D3. We conclude that vitamin D3, unlike retinoic acid, modifies keratin synthesis indirectly, by changing the differentiation phenotype of the keratinocyte.