Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease

Aim. To determine the diagnostic value of urinary excretion of type IV collagen in patients with type 1 diabetes with different stages of nephropathy.Methods. Urinary type IV collagen was determined in 60 patients with type 1 diabetes (23 with normal albuminuria, 28 with microalbuminuriaand 9 with macroalbuminuria) by an enzyme immunoassay. 10 healthy individuals were acted as the control group. Renal biopsy was performedin 22 patients. Deposits of type IV collagen were revealed by 11 individuals by immunohistochemistry. Results. The urinary excretion of type IV collagen increased with severety of diabetic nephropathy, correlating with the urinary albumin/creatinineratio, serum creatinine and parameters of daytime and nighttime systolic and diastolic blood pressure. Patients with excessive accumulation of typeIV collagen in the glomeruli had significantly higher level of type IV collagen in the urine. Conclusion. The determination of urinary type IV collagen can be used for early detection of renal fibrosis in patients with type 1 diabetes.

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Alport Syndrome: Clinical and Genetic Correlation in a Type-IV Collagen Disease

Hereditary Kidney Diseases - Contributions to Nephrology ◽

10.1159/000059879 ◽

1997 ◽

pp. 116-123 ◽

Cited By ~ 1

Author(s):

K.-O. Netzer ◽

O. Gross ◽

C. Jung ◽

R. Kirsten ◽

S. Seibold ◽

...

Keyword(s):

Genetic Correlation ◽

Alport Syndrome ◽

Type Iv Collagen ◽

Collagen Disease ◽

Type Iv

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Inhibitory effect of interleukin-1β on angiotensin II-induced connective tissue growth factor and type IV collagen production in cultured mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00129.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. F149-F160 ◽

Cited By ~ 37

Author(s):

Elsa Sánchez-López ◽

Juan Rodriguez-Vita ◽

Cecile Cartier ◽

Monica Rupérez ◽

Vanesa Esteban ◽

...

Keyword(s):

Extracellular Matrix ◽

Angiotensin Ii ◽

Growth Factor ◽

Renal Fibrosis ◽

Type Iv Collagen ◽

Mesangial Cells ◽

Tissue Growth ◽

Ang Ii ◽

Collagen Production ◽

Type Iv

Connective tissue growth factor (CTGF) is overexpressed in kidney diseases associated with extracellular matrix accumulation. Angiotensin II (ANG II) participates in renal fibrosis by the upregulation of growth factors, including CTGF, and extracellular matrix proteins, such as type IV collagen. During renal injury, ANG II and the macrophage-produced cytokine interleukin-1β (IL-1β) may be present simultaneously in the glomerular environment. However, there are no studies about the interaction between ANG II and IL-1β in renal fibrosis. For this reason, in cultured mesangial cells (MC), we investigated whether IL-1β could regulate ANG II-mediated collagen accumulation and the mechanisms underlying this process. In MC, CTGF is a downstream mediator of type IV collagen production induced by ANG II. IL-1β did not increase the production of CTGF and type IV collagen but significantly inhibited ANG II-induced CTGF and type IV collagen overexpression. Moreover, IL-1β also inhibited type IV collagen upregulation caused by exogenous recombinant CTGF. Matrix metalloproteinase-9 (MMP-9) is the main enzyme involved in type IV collagen degradation. In MC, coincubation of IL-1β and ANG II caused a synergistic increase in MMP-9 gene expression and activity, associated with type IV collagen inhibition. The described IL-1β effects were dependent on activation of ERK/MAPK but independent p38-MAPK, JNK, phosphatidylinositol 3-kinase/Akt, and Rho-associated kinase pathways. In summary, these data indicate that IL-1β inhibited ANG II-mediated type IV collagen production, via CTGF downregulation, and increased type IV collagen degradation, through MMP-9 upregulation. Our in vitro data show that the proinflammatory cytokine IL-1β abrogates ANG II-induced CTGF production, describing antagonistic activities of proinflammatory cytokines on ANG II actions.

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Sodium-glucose cotransporter 2 inhibition prevents renal fibrosis in cyclosporine nephropathy

Acta Diabetologica ◽

10.1007/s00592-021-01681-2 ◽

2021 ◽

Author(s):

Giovanna Castoldi ◽

Raffaella Carletti ◽

Silvia Ippolito ◽

Massimiliano Colzani ◽

Francesca Barzaghi ◽

...

Keyword(s):

Blood Pressure ◽

Tyrosine Hydroxylase ◽

Renal Fibrosis ◽

Type Iv Collagen ◽

Interstitial Fibrosis ◽

Experimental Period ◽

Type I ◽

Collagen Expression ◽

Type Iv ◽

Inflammatory Infiltrates

Abstract Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes. Methods Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection, n = 8) and CsA plus empagliflozin (Empa, 10 mg/kg/day, per os, n = 7) were administered for 4 weeks. The control groups were treated with placebo (Control, n = 7) or empagliflozin (Control + Empa, n = 5). Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental period. At the end of the experimental protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages), type I and type IV collagen expression, and tyrosine hydroxylase expression, used as marker of sympathetic nerve activity. Results CsA-treated rats showed a significant increase (p < 0.01) in blood pressure, which was reduced by administration of empagliflozin (p < 0.05). CsA administration caused an increase in glomerular and tubulo-interstitial fibrosis (p < 0.05), renal inflammatory infiltrates (p < 0.05), type I and type IV collagen expression (p < 0.01), and tyrosine hydroxylase expression (p < 0.01) as compared to the control rats and control + Empa-treated rats. Treatment with empagliflozin in CsA-treated rats reduced glomerular (p < 0.01) and tubulo-interstitial fibrosis (p < 0.05), type I and type IV collagen expression (p < 0.01), inflammatory cell infiltration (p < 0.01) and tyrosine hydroxylase expression (p < 0.05), as compared to rats treated with CsA. Conclusion Empagliflozin administration caused a reduction in blood pressure in CsA-treated rats and showed a protective effect on CsA nephropathy by decreasing renal fibrosis, type I and type IV collagen expression, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that empagliflozin promotes nephroprotection also in non-diabetic kidney disease.

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The use of 1nm silver enhanced gold probes for the detection of skin antigens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162077 ◽

1990 ◽

Vol 48 (3) ◽

pp. 902-903

Author(s):

J.P Cassella ◽

H. Shimizu ◽

A. Ishida-Yamamoto ◽

R.A.J. Eady

Keyword(s):

Type Iv Collagen ◽

Freeze Substitution ◽

Collagen Type Iv ◽

Electron Microscopic ◽

Normal Human Skin ◽

Type Iv ◽

Type Vii Collagen ◽

Keratin Filaments ◽

Normal Human ◽

Phosphate Buffered Saline

1nm colloidal gold with silver enhancement has been used in conjunction with a low-temperature post-embedding (post-E) technique for the demonstration of skin antigens at both the light microscopic (LM) and electron microscopic (EM) levels.Keratin filaments and basement membrane zone (BMZ) associated antigens in normal human skin (NHS) were immunolabelled using antibodies against keratin 14, 10, and 1, the carboxy-terminus and collagenous portion of type VII collagen, type IV collagen and bullous pemphigoid antigen (BP-Ag).Fresh samples of NHS were cryoprotected in 15% glycerol, cryofixed in propane at -190°C, subjected to freeze substitution in methanol at -80°C and embedded in Lowicryl K11M at -60°C. Polymerisation of the resin was initiated under UVR at - 60°C for 48 hours and continued at room temperature for a further 48 hours. Semith in sections were air dried onto slides coated with 3-aminopropyltriethoxysilane. The following immunolabelling protocol was adopted: Primary antibody was applied for 2 hours at 37°C or overnight at 4°C. Following washing in Dulbecco’s phosphate buffered saline (PBSA) a biotinylated secondary antibody was applied for 2 hours at 37°C. The sections were further washed in PBSA and 1nm gold avidin was applied. Sections were finally washed in PBSA and silver enhanced.

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