Результаты поиска

Cystatin M / E expression in inflammatory and neoplastic skin disorders.

BACKGROUND: Cystatins are natural and specific inhibitors of endogenous mammalian lysosomal cysteine proteinases and exogenous microbial cysteine proteinases. Cystatins were shown to provide regulatory and protective functions against uncontrolled proteolysis in several disease processes. Recently we reported that cystatin M/E, which is a novel member of the cystatin gene family, has an unusually restricted expression pattern that is limited to skin. Although cystatin M/E possesses two distinct biochemical properties (it is a proteinase inhibitor and a substrate for transglutaminase) its physi…

Cystatin M/E Ameliorates Multiple Myeloma-Induced Hyper Osteolytic Bone Resorption.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Совпадение в полном тексте источника
… Recently, we combined PET-CT scanning with global gene expression profiling of BM CD138-selected plasma cells (PC) from 512 newly diagnosed MM patients to show that the absence of osteolytic lesions is linked to elevated expression of cystatin M/E (CST6), a cysteine protease inhibitor, secreted by MM … Cystatin M loss is associated with the losses of estrogen receptor, progesterone receptor, and HER4 in invasive breast cancer Breast Cancer Res. 2010 12 R100 10.1186/bcr2783 21092257 PMC3046445 19. Tsukasaki M. Huynh N.C. Okamoto K. Muro R. Terashima A. Kurikawa Y. Komatsu N. Pluemsakunthai W. …

Cystatin M/E ameliorates bone resorption through increasing osteoclastic cell estrogen influx.

In multiple myeloma (MM), increased osteoclast differentiation leads to the formation of osteolytic lesions in most MM patients. Bisphosphonates, such as zoledronic acid (ZA), are used to ameliorate bone resorption, but due to risk of serious side effects as well as the lack of repair of existing lesions, novel anti-bone resorption agents are required. Previously, the absence of osteolytic lesions in MM was strongly associated with elevated levels of cystatin M/E (CST6), a cysteine protease inhibitor, secreted by MM cells. In this study, both MM- and ovariectomy (OVX)-induced osteoporotic mous…

The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis.

Cystatin M/E is a recently discovered cysteine proteinase inhibitor whose expression is largely confined to cutaneous epithelia. In human skin it is expressed in sweat glands, hair follicles, and stratum granulosum of the epidermis where it presumably acts as a substrate for transglutaminase. Very recently we reported that a null mutation in the mouse cystatin M/E gene (Cst6) causes the murine ichq phenotype, which is characterized by abnormalities in cornification and desquamation, demonstrating an essential role for cystatin M/E in the final stages of epidermal differentiation. We here obtai…

Cathepsin B as a potential cystatin M/E target in the mouse hair follicle.

Deficiency of the cysteine protease inhibitor cystatin M/E (Cst6) in mice leads to disturbed epidermal cornification, impaired barrier function, and neonatal lethality. We report the rescue of the lethal skin phenotype of ichq (Cst6-deficient; Cst6-/-) mice by transgenic, epidermis-specific, reexpression of Cst6 under control of the human involucrin (INV) promoter. Rescued Tg(INV-Cst6)Cst6ichq/ichq mice survive the neonatal phase, but display severe eye pathology and alopecia after 4 mo. We observed keratitis and squamous metaplasia of the corneal epithelium, comparable to Cst6-/-Ctsl+/- mice,…

Identification, molecular profiling and immune functions of cystatin M in silver pomfret (Pampus argenteus).

Cystatins play an important role in various physiological and pathological processes of organisms, including regulating protein metabolism, antigen processing, inflammatory response, nutritional disorders, and controlling enzyme activity. However, research on immunity functions of fish cystatin M is limited. In this study, Pampus argenteus cystatin M (Pacystatin M) was identified and analyzed. Its amino acid sequence was highly conserved in teleosts, and included the conserved cystatin cysteine protease inhibitor motifs. Pacystatin M was highly expressed in the gill, spleen, and intestine, whe…

Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin.

PURPOSE: We aimed to assess the biological and clinical significance of the human cysteine protease inhibitor cystatin M/E, encoded by the CTS6 gene, in diseases of human hair and skin. METHODS: Exome and Sanger sequencing was performed to reveal the genetic cause in two related patients with hypotrichosis. Immunohistochemical, biophysical, and biochemical measurements were performed on patient skin and 3D-reconstructed skin from patient-derived keratinocytes. RESULTS: We identified a homozygous variant c.361C>T (p.Gln121*), resulting in a premature stop codon in exon 2 of CST6 associated wi…

Cystatin M/E Variant Causes Autosomal Dominant Keratosis Follicularis Spinulosa Decalvans by Dysregulating Cathepsins L and V.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare cornification disorder with an X-linked recessive inheritance in most cases. Pat … n line with family history, the variant was not present in samples from her parents. CST6 codes for cystatin M/E, a cysteine protease inhibitor. Patient keratinocytes showed increased expression of cathepsin genes CTSL and CTSV and reduced expression of transglutaminase genes TGM1 and TGM3. A relative gain of active, cleaved transglutaminases was found in pa …

Cystatin M loss is associated with the losses of estrogen receptor, progesterone receptor, and HER4 in invasive breast cancer.

INTRODUCTION: This study was aimed at understanding the clinicopathological significance of cystatin M loss, and investigating possible factors responsible for cystatin M loss in breast cancer. METHODS: The expression of estrogen receptor (ER), progesterone receptor (PR), HER2, HER4, and cystatin M was retrospectively analyzed using immunohistochemistry in 117 patients with ductal carcinoma in situ (DCIS) and in 175 patients with invasive breast cancer (IBC). The methylation status of CST6 gene encoding cystatin M was evaluated using methylation-specific polymerase chain reaction (PCR) in for…

Evidence that unrestricted legumain activity is involved in disturbed epidermal cornification in cystatin M/E deficient mice.

Homozygosity for Cst6 null alleles causes the phenotype of the ichq mouse, which is a model for human harlequin ichthyosis (OMIM 242500), a genetically heterogeneous group of keratinization disorders. Here we report evidence for the mechanism by which deficiency of the cysteine protease inhibitor cystatin M/E (the Cst6 gene product) leads to disturbed cornification, impaired barrier function and dehydration. Absence of cystatin M/E causes unrestricted activity of its target protease legumain in hair follicles and epidermis, which is the exact location where cystatin M/E is normally expressed. …

Cystatins C, E/M and F in human pleural fluids of patients with neoplastic and inflammatory lung disorders.

Secretory type 2 cystatins, like cystatins C, E/M and F, are thought to be involved in many pathobiological processes, including vascular amyloidosis, rheumatoid arthritis, Alzheimer's disease, osteoporosis, viral and bacterial infections, inflammatory disorders and tumour invasion and metastasis. In order to define the levels of cystatins C, E/M, and F in pleural effusions and to investigate whether these cystatins correlate with diagnostic parameters of pleural and lung diseases, we determined their concentrations in 160 pleural effusions. The median concentration of cystatin C in pleural ef

A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification.

Cystatin M/E (CST6 ), a new member of the cystatin gene family, has a restricted expression pattern in humans, which is largely limited to cutaneous epithelia. Although cystatin M/E possesses two distinct biochemical properties, being a cysteine proteinase inhibitor and a substrate for transglutaminase, its physiological function is unknown. Here we report the isolation and characterization of the mouse Cst6 orthologue and the assignment of the chromosomal localization to the proximal end of mouse chromosome 19. This region corresponds to the locus of the spontaneous harlequin ichthyosis (ichq…

Protease activity of legumain is inhibited by an increase of cystatin E/M in the DJ-1-knockout mouse spleen, cerebrum and heart.

Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Legumain activity has been detected in various mouse tissues including the kidney, spleen and epididymis. Legumain is overexpressed in the majority of human solid tumors and transcription of the legumain gene is regulated by the p53 tumor suppressor in HCT116 cells. The legumain activity is also increased under acid conditions in Alzheimer's disease brains. DJ-1/PARK7, a cancer- and Parkinson's disease-associated protein, works as a coactivator to various transcription factors, including the androgen receptor, p53, PSF, Nrf2, SREBP and R

Cystatin M/E expression is restricted to differentiated epidermal keratinocytes and sweat glands: a new skin-specific proteinase inhibitor that is a target for cross-linking by transglutaminase.

Using serial analysis of gene expression on cultured human keratinocytes we found high expression levels of genes putatively involved in host protection and defense, such as proteinase inhibitors and antimicrobial proteins. One of these expressed genes was the recently discovered cysteine proteinase inhibitor cystatin M/E that has not been characterized so far at the protein level with respect to tissue distribution and additional biologic properties. Here we report that cystatin M/E has a tissue-specific expression pattern in which high expression levels are restricted to the stratum granulos…

Purification and characterization of a new cystatin inhibitor from Taiwan cobra (Naja naja atra) venom.

Cobra cystatin, a new cysteine-proteinase inhibitor of the cystatin superfamily, was isolated from the venom of the Taiwan cobra (Naja naja … identical with other Type 2 cystatins, the most closely related being the recently described human cystatin M, which also has a similar five-residue insertion starting at position 76 (chicken cystatin numbering). A molecular phylogenetic tree of 16 representative members of Family 2 cystatins was constructed by parsimony analysis; it suggests that snake cys …

Cystatin C in diabetics as a marker of mild renal insufficiency after CABG.

PURPOSE: The purpose of this study was to evaluate the accuracy of plasma cystatin C in acute impairment in renal function; plasma cystatin C was compared to plasma creatinine in two hundred patients undergoing elective CABG surgery. METHODS: We performed a prospective clinical study of two hundred patients undergoing coronary bypass surgery. Plasma creatinine and cystatin C were measured preoperatively and on the first and fourth days after surgery. Estimated glomerular filtration rate (GFR) was calculated using one creatinine-based and two cystatin C-based equations. RESULTS: There were 14

Variability in Cystatin C- and Creatinine-estimated Glomerular Filtration Rate in Adults With Spina Bifida.

OBJECTIVE: To determine if serum cystatin C, which does not depend on muscle mass, is a potential alternative measure of kidney function in individuals with Spina Bifida and lower urinary tract dysfunction. Assessment using serum creatinine to estimate glomerular filtration rate is often compromised in this population because of decreased muscle mass from paralysis, which varies over spinal lesion levels and sub-phenotypes. We hypothesized creatinine-based formulas overestimate glomerular filtration rate at higher lesion levels relative to cystatin C-based formulas, and cystatin C-based equati

Applicability of Creatinine- and Cystatin C-Based Estimated Glomerular Filtration Rate Equations in Patients With Neurogenic Lower Urinary Tract Dysfunction.

OBJECTIVES: To assess the applicability of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and Chinese eGFR Investigation Collaboration (C-eGFR) equations in estimating glomerular filtration rate (GFR) in patients with neurogenic lower urinary tract dysfunction (NLUTD). These equations are based on serum creatinine, cystatin C, or combined creatinine and cystatin C. METHODS: This prospective study enrolled 142 adult patients with NLUTD. GFR was measured using the dual plasma ⁹⁹mTc-DTPA plasma clearance method. We compared the bias, precision, accuracy and correct classif

The relative effects of fat versus muscle mass on cystatin C and estimates of renal function in healthy young men.

BACKGROUND: It is well known that plasma creatinine concentration is affected by muscle mass, while some studies have suggested cystatin C is affected by body mass index (BMI). Our aim was to assess the effects of lean versus fat mass on cystatin C and creatinine derivative equations in estimating glomerular filtration rate (GFR) in healthy young men. METHODS: Three groups of participants were studied: those classified as normal (BMI 18-25 kg/m(2) with body fat <30%); muscular subjects (BMI >30 kg/m(2) and body fat <20%); and obese subjects (BMI >30 kg/m(2) and body fat >30%). All underwent d

Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children.

BACKGROUND: To compare estimated glomerular filtration rate (GFR) by Schwartz formula and cystatin C-derived formula in a large population of children with a large spectrum of renal disease. METHODS: Serum creatinine, cystatin C and estimated GFR were determined in 273 children, 254 with renal disease, and a mean age of 10.0+/-4.4 y. Nineteen children were used as control, with a mean age of 8.5+/-4.2 y. RESULTS: The children had nephrotic syndrome (16.5%), glomerulonephritis (11.4%), neurogenic bladder (11.4%), hydronephrosis (9.8%), asymptomatic hematuria (11%), chronic renal disease (5.9%