Abstract
Collagen is a major component of the extracellular matrix (ECM) and has an imminent role in fibrosis, in, among others, chronic kidney disease (CKD). Collagen alpha-1(I) (col1a1) is the most abundant collagen type and has previously been underlined for its contribution to the disease phenotype. Here, we examined 5000 urinary peptidomic datasets randomly selected from healthy participants or patients with CKD to identify urinary col1a1 fragments and study their abundance, position in the main protein, as well as their correlation with renal function. We identified 707 col1a1 peptides that differed in their amino acid sequence and/or post-translational modifications (hydroxyprolines). Well-correlated peptides with the same amino acid sequence, but a different number of hydroxyprolines, were combined into a final list of 503 peptides. These 503 col1a1 peptides covered 69% of the full col1a1 sequence. Sixty-three col1a1 peptides were significantly and highly positively associated (rho > +0.3) with the estimated glomerular filtration rate (eGFR), while only six peptides showed a significant and strong, negative association (rho < −0.3). A similar tendency was observed for col1a1 peptides associated with ageing, where the abundance of most col1a1 peptides decreased with increasing age. Collectively the results show a strong association between collagen peptides and loss of kidney function and suggest that fibrosis, potentially also of other organs, may be the main consequence of an attenuation of collagen degradation, and not increased synthesis.
Highlights
IntroductionThe collagen family consists of 28 different members and is the most abundant protein family in mammals [1,2]
This article is an open access articleThe collagen family consists of 28 different members and is the most abundant protein family in mammals [1,2]
Urinary peptidomics data based on coupled to mass spectrometry (CE-MS) technology were extracted from the Human
Summary
The collagen family consists of 28 different members and is the most abundant protein family in mammals [1,2]. About 30% of the human proteome is collagens, with this percentage being substantially higher in certain areas of the body (e.g., tendons) [3]. Of total human collagen comprises collagen type I [4]. Collagen type I is present in almost all connective tissues. It is the interstitial matrix collagen, organized in fibrils, that plays an distributed under the terms and conditions of the Creative Commons. Important role in the structure of different tissues. Several post-translational modifications (PTMs) that underlie collagen type I, among which, hydroxylation of proline and lysine, as well as the glycosylation of the hydroxylated latter, occur during translation [1]
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