Targeting Collagen Type III in Proteinuric Kidney Disease: Informing Drug Potential Using the Jaccard–Tanimoto Index

Collagenofibrotic glomerulopathy, a collagen type III kidney disease, is associated with proteinuria and accumulation ofcollagen type III in the glomerulus specifically the mesangium and/or capillary walls. The puromcyin aminonucleoside (PAN) nephropathy model was evaluated to examine the relation between COL3A1 mRNA and proteinuria. In Wistar rats administered PAN, a robust increase in proteinuria was accompanied by glomerular hypertrophy and expansion of both the Bowman’s capsule and Bowman’s space. An ~4-fold increase in renal COL3A1 mRNA was observed in the PAN cohort with urine protein exhibiting a direct (r = 0.8) and significant correlation with kidney COL3A1 mRNA level. Both Picrosirius red polarized microscopy and immunohistochemical analysis showed localization of collagen type III to the glomerular mesangium. Gene ontology-driven transcriptomic analysis reveals a robust COL3A1 network in the glomerular compartment.

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The immunohistochemical analysis of fibronectin, collagen type III, laminin, and cytokeratin 5 in putrified skin

Forensic Science International ◽

10.1016/0379-0738(93)90247-8 ◽

1993 ◽

Vol 61 (1) ◽

pp. 35-42 ◽

Cited By ~ 13

Author(s):

P. Betz ◽

A. Nerlich ◽

J. Wilske ◽

J. Tübel ◽

R. Penning ◽

...

Keyword(s):

Collagen Type ◽

Immunohistochemical Analysis ◽

Collagen Type Iii ◽

Type Iii ◽

Cytokeratin 5

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Diagnosis of Collagen Type III Glomerulopathy Using Picrosirius Red and PASH/Masson’s Trichrome Stain

Veterinary Pathology ◽

10.1177/0300985820934111 ◽

2020 ◽

Vol 57 (5) ◽

pp. 675-680

Author(s):

Katelin L. Davis ◽

Anne L. Burnum ◽

Jessica A. Beck ◽

Shannon G. M. Kirejczyk ◽

Margaret A. Miller ◽

...

Keyword(s):

Light Microscopy ◽

Collagen Type ◽

Type Iii Collagen ◽

Fibrillar Collagen ◽

Collagen Type Iii ◽

Type Iii ◽

Glomerular Capillary ◽

Collagen Type Iii Glomerulopathy ◽

Picrosirius Red ◽

Capillary Walls

Canine collagen type III glomerulopathy (Col3GP) is a rare juvenile nephropathy in which irregular type III collagen fibrils and fibronectin accumulate in glomerular capillary walls and the mesangium. Necropsy findings were reviewed from 5 puppies diagnosed with Col3GP at 6 to 18 weeks of age. Histologically, with hematoxylin and eosin stain, the glomerular capillary walls and mesangium were diffusely and globally expanded by homogeneous pale eosinophilic material. Ultrastructurally, the subendothelial zone and mesangium were expanded by fibronectin and cross-banded collagen type III fibrils, diagnostic of Col3GP. Two additional stains were employed to identify the material within glomeruli as fibrillar collagen using light microscopy. In all 5 cases, the material was red with picrosirius red and birefringent under polarized light, and was blue with periodic acid-Schiff/hematoxylin/trichrome (PASH/TRI), thereby identifying it as fibrillar collagen. Based on these unique staining characteristics with picrosirius red and PASH/TRI, Col3GP may be reliably diagnosed with light microscopy alone.

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Comparison of the solophenyl-red polarization method and the immunohistochemical analysis for collagen type III

International Journal of Legal Medicine ◽

10.1007/bf01371233 ◽

1992 ◽

Vol 105 (1) ◽

pp. 27-29 ◽

Cited By ~ 7

Author(s):

P. Betz ◽

A. Nerlich ◽

J. Wilske ◽

I. Wiest ◽

R. Penning ◽

...

Keyword(s):

Collagen Type ◽

Immunohistochemical Analysis ◽

Collagen Type Iii ◽

Polarization Method ◽

Type Iii

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SUN-152 DIFFERENCES IN COLLAGEN TYPE III TURNOVER IN ACUTE AND CHRONIC RODENT MODELS OF KIDNEY DISEASE

Kidney International Reports ◽

10.1016/j.ekir.2020.02.681 ◽

2020 ◽

Vol 5 (3) ◽

pp. S263

Author(s):

N. SPARDING ◽

A. Møller ◽

D. G. K. Rasmussen ◽

P. Mose Nielsen ◽

R. S. Hijmans ◽

...

Keyword(s):

Kidney Disease ◽

Collagen Type ◽

Rodent Models ◽

Collagen Type Iii ◽

Type Iii

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Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients

Clinical Kidney Journal ◽

10.1093/ckj/sfz174 ◽

2020 ◽

Author(s):

Federica Genovese ◽

Daniel Guldager Kring Rasmussen ◽

Morten A Karsdal ◽

Mark Jesky ◽

Charles Ferro ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Progression ◽

Collagen Type ◽

Pathological Feature ◽

Collagen Type Iii ◽

Ckd Progression ◽

Type Iii ◽

Ckd Stage ◽

Fibrotic Scar

Abstract Background Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the relationship between fragments reflecting active formation (PRO-C3) and degradation (C3M) of COL3 and CKD disease progression and mortality in a prospective cohort of CKD patients. Methods We measured PRO-C3 and C3M in urine (uPRO-C3 and uC3M) and serum (sPRO-C3 and sC3M) of 500 patients from the Renal Impairment in Secondary Care study. Disease progression was defined as a decline in estimated glomerular filtration rate >30% or the start of renal replacement therapy within 12 and 30 months. Results Levels of uC3M/creatinine decreased, whereas levels of uPRO-C3/creatinine and sPRO-C3 increased with increasing CKD stage. uC3M/creatinine was inversely and independently associated with disease progression by 12 months {odds ratio [OR] 0.39 [95% confidence interval (CI) 0.18–0.83]; P = 0.01 per doubling of uC3M/creatinine} with development of end-stage renal disease [hazard ratio (HR) 0.70 (95% CI 0.50–0.97); P = 0.03 per doubling of uC3M/creatinine]. sPRO-C3 at baseline was independently associated with increased mortality [HR 1.93 (95% CI 1.21–3.1); P = 0.006 per doubling of sPRO-C3] and disease progression by 30 months [OR 2.16 (95% CI 1.21–3.84); P = 0.009 per doubling of sPRO-C3]. Conclusions Dynamic products of COL3 formation and degradation were independently associated with CKD progression and mortality and may represent an opportunity to link pathological processes with targeted treatments against fibrosis.

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Data mining-based study of collagen type III alpha 1 (COL3A1) prognostic value and immune exploration in pan-cancer

Bioengineered ◽

10.1080/21655979.2021.1949838 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3634-3646

Author(s):

Hanyu Zhang ◽

Cheng Ding ◽

Yatong Li ◽

Cheng Xing ◽

Shunda Wang ◽

...

Keyword(s):

Data Mining ◽

Prognostic Value ◽

Collagen Type ◽

Collagen Type Iii ◽

Type Iii ◽

Pan Cancer

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Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

Scientific Reports ◽

10.1038/s41598-020-79608-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neel I. Nissen ◽

Stephanie Kehlet ◽

Mogens K. Boisen ◽

Maria Liljefors ◽

Christina Jensen ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Collagen Type ◽

Performance Status ◽

Drug Uptake ◽

Collagen Type Iii ◽

Serum Samples ◽

Type Iii ◽

Poor Treatment ◽

And Performance

AbstractA desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

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