scholarly journals Collagen type III and VI remodeling biomarkers are associated with kidney fibrosis in lupus nephritis

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0001132021
Author(s):  
Federica Genovese ◽  
Ahmad Akhgar ◽  
S. Sam Lim ◽  
Alton B. Farris ◽  
Monica Battle ◽  
...  

Background: Lupus nephritis (LN) occurs in up to 40% of patients with systemic lupus erythematosus (SLE). Reliable biomarkers of kidney damage are needed to identify SLE patients at risk to develop LN in order to improve screening, treat earlier, and halt progression to kidney failure. Novel biomarkers of extracellular matrix remodeling were evaluated as markers of kidney fibrosis and disease activity in LN patients. Methods: Biomarkers of the interstitial collagen type III (PRO-C3) and type VI (PRO-C6) formation as well as of collagen type III (C3M) degradation were evaluated in the serum and urine of 40 patients with LN, 20 SLE patients without LN, 20 healthy controls and 10 biopsy controls (histological kidney inflammation/damage without SLE). Their association with histological markers of interstitial fibrosis and tubular atrophy, with inflammatory cell infiltration and with disease activity and chronicity in the LN patients was assessed. Results: Despite PRO-C3 (serum) and PRO-C6 (serum and urine) were significantly elevated in LN patients compared to healthy controls, they were not able to separate the LN from the SLE patients. C3M (urine) levels were not different in the LN group compared to the others. C3M (urine) strongly correlated and PRO-C6 (serum and urine) inversely correlated with kidney function (eGFR). The biomarkers of interstitial collagen turnover PRO-C6 (serum) and C3M (urine) correlated with histological markers of interstitial fibrosis, tubular atrophy, and monocyte infiltration. Conclusions: Non-invasive collagen turnover biomarkers are promising tools to identify SLE patients with kidney histological modifications.

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Federica Genovese ◽  
Ahmad Akhgar ◽  
Alton B Farris Iii ◽  
Sam S Lim ◽  
Monica Battle ◽  
...  

2010 ◽  
Vol 298 (3) ◽  
pp. H1003-H1013 ◽  
Author(s):  
Jorge F. Giani ◽  
Marina C. Muñoz ◽  
Marcos A. Mayer ◽  
Luciana C. Veiras ◽  
Cristina Arranz ◽  
...  

The present study examined whether chronic treatment with angiotensin (ANG)-(1–7) reduces cardiac remodeling and inhibits growth-promoting signaling pathways in the heart of fructose-fed rats (FFR), an animal model of insulin resistance. Sprague-Dawley rats were fed either normal rat chow (control) or the same diet plus 10% fructose in drinking water. For the last 2 wk of a 6-wk period of the corresponding diet, control and FFR were implanted with osmotic pumps that delivered ANG-(1–7) (100 ng·kg−1·min−1). A subgroup of each group of animals (control or FFR) underwent a sham surgery. We determined heart weight, myocyte diameter, interstitial fibrosis, and perivascular collagen type III deposition as well as the phosphorylation degree of ERK1/2, JNK1/2, and p38MAPK. FFR showed a mild hypertension that was significantly reduced after ANG-(1–7) treatment. Also, FFR displayed higher ANG II circulating and local levels in the heart that remained unaltered after chronic ANG-(1–7) infusion. An increased heart-to-body weight ratio, myocyte diameter, as well as left ventricular fibrosis and perivascular collagen type III deposition were detected in the heart of FFR. Interestingly, significant improvements in these cardiac alterations were obtained after ANG-(1–7) treatment. Finally, FFR that received ANG-(1–7) chronically displayed significantly lower phosphorylation levels of ERK1/2, JNK1/2, and p38MAPK. The beneficial effects obtained by ANG-(1–7) were associated with normal values of Src-homology 2-containing protein-tyrosine phosphatase-1 (SHP-1) activity in the heart. In conclusion, chronic ANG-(1–7) treatment ameliorated cardiac hypertrophy and fibrosis and attenuated the growth-promoting pathways in the heart. These findings show an important protective role of ANG-(1–7) in the heart of insulin-resistant rats.


Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 3634-3646
Author(s):  
Hanyu Zhang ◽  
Cheng Ding ◽  
Yatong Li ◽  
Cheng Xing ◽  
Shunda Wang ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neel I. Nissen ◽  
Stephanie Kehlet ◽  
Mogens K. Boisen ◽  
Maria Liljefors ◽  
Christina Jensen ◽  
...  

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.


2007 ◽  
Vol 50 (6) ◽  
pp. 1037-1042 ◽  
Author(s):  
Nan Chen ◽  
Xiaoxia Pan ◽  
Yaowen Xu ◽  
Zhaohui Wang ◽  
Hao Shi ◽  
...  

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.


2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Efstathios Vassiliadis ◽  
Sanne Skovgård Veidal ◽  
Natasha Barascuk ◽  
Jhinuk Basu Mullick ◽  
Rikke Elgaard Clausen ◽  
...  

Author(s):  
Cheng Hu ◽  
Wenqi Liu ◽  
Linyu Long ◽  
Zhicun Wang ◽  
Yihui Yuan ◽  
...  

Correction for ‘Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds’ by Cheng Hu et al., J. Mater. Chem. B, 2021, 9, 9684–9699, DOI: 10.1039/D1TB02170B.


Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2973
Author(s):  
Rory Gibney ◽  
Jennifer Patterson ◽  
Eleonora Ferraris

The development of commercial collagen inks for extrusion-based bioprinting has increased the amount of research on pure collagen bioprinting, i.e., collagen inks not mixed with gelatin, alginate, or other more common biomaterial inks. New printing techniques have also improved the resolution achievable with pure collagen bioprinting. However, the resultant collagen constructs still appear too weak to replicate dense collagenous tissues, such as the cornea. This work aims to demonstrate the first reported case of bioprinted recombinant collagen films with suitable optical and mechanical properties for corneal tissue engineering. The printing technology used, aerosol jet® printing (AJP), is a high-resolution printing method normally used to deposit conductive inks for electronic printing. In this work, AJP was employed to deposit recombinant human collagen type III (RHCIII) in overlapping continuous lines of 60 µm to form thin layers. Layers were repeated up to 764 times to result in a construct that was considered a few hundred microns thick when swollen. Samples were subsequently neutralised and crosslinked using EDC:NHS crosslinking. Nanoindentation and absorbance measurements were conducted, and the results show that the AJP-deposited RHCIII samples possess suitable mechanical and optical properties for corneal tissue engineering: an average effective elastic modulus of 506 ± 173 kPa and transparency ≥87% at all visible wavelengths. Circular dichroism showed that there was some loss of helicity of the collagen due to aerosolisation. SDS-PAGE and pepsin digestion were used to show that while some collagen is degraded due to aerosolisation, it remains an inaccessible substrate for pepsin cleavage.


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