Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes

2018 ◽  
Vol 154 (1) ◽  
pp. 30-36
Author(s):  
Ang Li ◽  
Er-Zhi Gao ◽  
Ying-Xia Cui ◽  
Jian-Hong Liu ◽  
Xing Lv ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Collagen Type ◽  
Kidney Diseases ◽  
Collagen Type Iv ◽  
Bioinformatics Analyses ◽  
Thin Basement Membrane Nephropathy ◽  
Disease Phenotypes ◽  
Type Iv ◽  
Novel Variants ◽  
Pedigree Verification

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

Release of collagen type IV degrading activity from C6 astrocytoma cells and cell density

1996 ◽  
Vol 84 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
Masashi Tamaki ◽  
Warren McDonald ◽  
Rolando F. Del Maestro
Keyword(s):  
Cell Density ◽  
Collagen Type ◽  
Cell Communication ◽  
Collagen Type Iv ◽  
Major Protein ◽  
Content Type ◽  
Type Iv ◽  
Astrocytoma Cells ◽  
C6 Astrocytoma

✓ Type IV collagen is a major protein component of the vascular basement membrane and its degradation is crucial to the initiation of tumor-associated angiogenesis. The authors have investigated the influence of cell density on the release of collagen type IV degrading activity by C6 astrocytoma cells in monolayer culture. The release of collagen type IV degrading activity was assessed biochemically, immunocytochemically, and by Western blot analysis. The results demonstrate that increasing plating density and increasing cell density are associated with decreased collagen type IV degrading activity released per tumor cell. These findings indicate the existence of regulatory mechanisms dependent on cell—cell communication, which modulate release of collagen type IV degrading activity. The extrapolation of these results to the in vivo tumor microenvironment would suggest that individual and/or small groups of invading tumor cells, distant from the main tumor mass, would release substantial collagen type IV degrading activity, which may be crucial to their continued invasion and to angiogenesis.

Collagen type IV in acute rejection of kidney

2000 ◽  
Vol 32 (7) ◽  
pp. 1785 ◽  
Author(s):  
K Utsumi ◽  
T Sawada ◽  
E Adachi ◽  
S Horita ◽  
T Tojimbara ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Collagen Type ◽  
Collagen Type Iv ◽  
Type Iv

EOSINOPHILIC GASTRITIS IN CHILDREN: MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL DIAGNOSTIC CRITERIA

2021 ◽  
Vol 74 (7) ◽  
pp. 1722-1727
Author(s):  
Vira I. Bobrova ◽  
Anastasia O. Horobets ◽  
Julia I. Proshchenko ◽  
Ludmila O. Levadna ◽  
Zoriana V. Selska
Keyword(s):  
Lamina Propria ◽  
Collagen Type ◽  
Morphological Changes ◽  
Prognostic Index ◽  
Lymphocytic Infiltration ◽  
Eosinophilic Infiltration ◽  
Nuclear Antigen ◽  
Collagen Type Iv ◽  
Eosinophilic Gastritis ◽  
Type Iv

The aim: To study peculiarities of morphological and immunohistochemical changes of stomach’s mucosa in eosinophilic gastritis in children Materials and methods: 64.1±6.0% patients with eosinophilic gastritis and 35.9±6.0% patients with lymphocytic gastritis participated in our investigation. In order to verify the diagnosis morphological and immunohistochemical diagnostics of the stomach’s mucosa was performed in all children. To assess morphological changes in tissues the specimens were colored with hematoxylin, eosin and picrofuchsin by van Gieson’s. Indirect streptavidin-peroxydase staining method was used for immunohistochemical investigation and the following indexes were assessed: proliferating cell nuclear antigen – PCNA, Bcl – 2, Вax, Collagen Type ІV, TGFβ and NF-κβ. Results: Comparative analysis of morphologic investigation has demonstrated that eosinophilic gastritis is characterized by fibrosis and fibroblasts proliferation into basal and superficial parts of mucosa’s lamina propria, multiple hemorrhages, thrombosis and erosions on the background of eosinophilic infiltration. Immunohistochemical indexes of cellular restoration in eosinophilic gastritis are characterized by increased proliferative activity and decreased indexes of proapoptotic and antiapoptotic activity. Prevalence of the reaction with the use of monoclonal antibodies to Collagen Type IV in majority of children with eosinophilic gastritis was characterized by separate fragmented foci in basal membranes of superficial epithelium. Remarkable TGFβ immune coloration was detected in majority of children on the background of fibrosis and eosinophilic infiltration of lamina propria. NF-κβ expression in epitheliocytes’ cytoplasm and nuclei was uneven. Homogenous remarkable coloration was detected in majority of patients with lymphocytic infiltration of mucosa. Conclusions: Eosinophilic gastritis course in children is characterized by remarkable inflammation, decreased regeneration of the mucosa, impairment of cellular restoration which is prognostic index of fibrous remodeling development.

Glycated albumin stimulation of PKC-β activity is linked to increased collagen IV in mesangial cells

1999 ◽  
Vol 276 (5) ◽  
pp. F684-F690 ◽  
Author(s):  
Margo P. Cohen ◽  
Fuad N. Ziyadeh ◽  
Gregory T. Lautenslager ◽  
Jonathan A. Cohen ◽  
Clyde W. Shearman
Keyword(s):  
Collagen Type ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glycated Albumin ◽  
Matrix Proteins ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Pkc Β ◽  
Tgf Β1 ◽  
Stimulation Of

Albumin modified by Amadori-glucose adducts induces coordinate increases in the expression of extracellular matrix proteins, transforming growth factor (TGF)-β1, and the TGF-β type II receptor in glomerular mesangial cells. Because activation of protein kinase C (PKC) accompanies the increased mesangial cell expression of matrix proteins and TGF-β1 induced by high ambient glucose, we postulated that glycated albumin (GA) modulates PKC activity and that PKC participates in mediating the GA-induced stimulation of matrix production. To test this hypothesis, we examined the effects of PKC inhibitors on collagen type IV production by mouse or rat mesangial cells incubated with GA, and the influence of GA on PKC activity in these cells. Increased collagen type IV production evoked by GA in 5.5 and 25 mM glucose in mouse mesangial cells was prevented by both general (GF-109203X) and β-specific (LY-379196) PKC inhibitors. Total PKC activity, measured by phosphorylation of a PKC-specific substrate, increased with time after exposure of rat mesangial cells to GA compared with the nonglycated, glucose-free counterpart. GA caused an increase in PKC-β1 membrane-bound fraction and in total PKC activity in media containing physiological (5.5 mM) glucose concentrations in rat mesangial cells, confirming that the glucose-modified protein, and not a “hyperglycemic” milieu, was responsible. The findings indicate that Amadori-modified albumin stimulates mesangial cell PKC activity, and that activation of the PKC-β isoform is linked to the stimulation of collagen type IV production.

scholarly journals Protein Truncating Variants of colA in Clostridium perfringens Type G Strains

2021 ◽  
Vol 11 ◽  
Author(s):  
Lore Van Damme ◽  
Natasja Cox ◽  
Chana Callens ◽  
Michelle Dargatz ◽  
Monika Flügel ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Collagen Type ◽  
Gelatin Zymography ◽  
Relative Activity ◽  
Full Length ◽  
Collagen Type Iv ◽  
Type I ◽  
Necrotic Enteritis ◽  
Variant Type ◽  
Type Iv

Extracellular matrix (ECM) degrading enzymes produced by Clostridium perfringens may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry in the intestinal mucosa and destruction of the tissue. C. perfringens is known to produce several ECM-degrading proteases, such as kappa toxin, an extracellular collagenase that is encoded by the colA gene. In this study, the colA gene sequence of a collection of 48 C. perfringens strains, including pathogenic (i.e. toxinotype G) and commensal (i.e. toxinotype A) chicken derived strains and strains originating from other host species, was analyzed. Although the colA gene showed a high level of conservation (>96% nucleotide sequence identity), several gene variants carrying different nonsense mutations in the colA gene were identified, leading to the definition of four truncated collagenase variant types (I-IV). Collagenase variant types I, III and IV have a (nearly) complete collagenase unit but lack parts of the C-terminal recruitment domains, whereas collagenase variant types II misses the N-terminal part of collagenase unit. Gene fragments encoding a truncated collagenase were mainly linked with necrotic enteritis associated C. perfringens type G strains with collagenase variant types I and II being the most prevalent types. Gelatin zymography revealed that both recombinant full-length and variant type I collagenase have active auto-cleavage products. Moreover, both recombinant fragments were capable of degrading type I as well as type IV collagen, although variant type I collagenase showed a higher relative activity against collagen type IV as compared to full-length collagenase. Consequently, these smaller truncated collagenases might be able to break down collagen type IV in the epithelial basement membrane of the intestinal villi and so contribute to the initiation of the pathological process leading to necrotic enteritis.

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