Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Sep;67(9):643-661.
doi: 10.1369/0022155419849388. Epub 2019 May 22.

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

Roman David Bülow  1 , Peter Boor  1   2
Affiliations
Review

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

Roman David Bülow et al. J Histochem Cytochem. 2019 Sep.

Abstract

Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

Keywords: biomarker; bioprinting; chronic kidney disease; decellularization; extracellular matrix; fibrosis; tissue engineering; transforming growth factor beta.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Glomerular ECM components and changes during glomerulosclerosis. A schematic of a healthy glomerulus (A) and a glomerulus with nodular or focal segmental glomerulosclerosis (B) with description of the major ECM-components and their alterations in fibrosis in the mesangial ECM, the glomerular basement membrane and the Bowman’s capsule are shown. Apart from increased Collagen IV- and LKIV69-positivity, little is known on the exact composition of the Bowman’s capsule and the ECM forming FSGS lesions, albeit the ECM of FSGS is likely similar to the ECM of Bowman’s capsule, as it is mainly produced by the parietal epithelial cells. The right panel shows representative PAS stained human sections. (B): PAS-Stain was provided by Dr. Cannata-Ortiz. Scale bars indicate 50 µm. Abbreviations: BC, Bowman’s capsule; PAS, periodic acid-Schiff; FSGS, focal segmental glomerulosclerosis; ECM, extracellular matrix; HSPGs, heparan sulfate proteoglycans.
Figure 2.
Figure 2.
Tubulo-interstitial ECM components and changes during fibrosis. A schematic of a healthy (A) and fibrotic tubulo-interstitium (B) with description of the major ECM-components and their alterations in fibrosis in the interstitial ECM, the tubular and the peritubular capillary basement membranes are shown. The exact composition of the basement membrane of peritubular capillaries has not been investigated. Alterations of the basement membrane of peritubular capillaries are best appreciated by electron microscopy. The right panel shows representative PAS stained human sections. Scale bars indicate 50µm. Abbreviation: ECM, extracellular matrix; PAS, periodic acid-Schiff.
Figure 3.
Figure 3.
Vascular ECM components and changes during arteriosclerosis. A schematic of a healthy (A) and sclerotic renal arterial vessels (B) with description of the major ECM-components and their alterations in arteriosclerosis in the intima/neointima, media and adventitia are shown. Little is known on specific changes of adventitia in renal fibrosis. The right panel shows representative PAS stained human sections. Scale bars indicate 50µm. Abbreviation: ECM, extracellular matrix; PAS, periodic acid-Schiff.
Figure 4.
Figure 4.
Hallmarks of renal interstitial fibrosis. Immunohistochemical staining of ECM components shows prominent upregulation of collagen I (A), collagen III (B), and fibronectin (C) in interstitial fibrosis compared to healthy mice. Scale bars indicate 50 µm. Abbreviation: ECM, extracellular matrix.
See this image and copyright information in PMC

References

    1. Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, Hobbs FD. Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS ONE. 2016;11(7):e0158765. doi:10.1371/journal.pone.0158765. - DOI - PMC - PubMed
    1. Neovius M, Jacobson SH, Eriksson JK, Elinder CG, Hylander B. Mortality in chronic kidney disease and renal replacement therapy: a population-based cohort study. BMJ Open. 2014;4(2):e004251. doi:10.1136/bmjopen-2013-004251. - DOI - PMC - PubMed
    1. Michael AF. The glomerular mesangium. Contrib Nephrol. 1984;40:7–16. - PubMed
    1. Lennon R, Byron A, Humphries JD, Randles MJ, Carisey A, Murphy S, Knight D, Brenchley PE, Zent R, Humphries MJ. Global analysis reveals the complexity of the human glomerular extracellular matrix. J Am Soc Nephrol. 2014;25(5):939–51. doi:10.1681/ASN.2013030233. - DOI - PMC - PubMed
    1. Xu J, Shi GP. Vascular wall extracellular matrix proteins and vascular diseases. Biochim Biophys Acta. 2014;1842(11):2106–119. doi:10.1016/j.bbadis.2014.07.008. - DOI - PMC - PubMed

Publication types

LinkOut - more resources