Collagen constitutes about twelve percent in females and seventeen percent in males of the total protein in mice

Abstract

Collagen has been postulated to be the most abundant protein in our body, making up one-third of the total protein content in mammals. However, to the best of our knowledge, a direct assessment of the total collagen levels of an entire mammal to confirm this estimate is missing. Here we measured hydroxyproline levels as a proxy for collagen content together with total protein levels of entire mice or of individual tissues. Collagen content normalized to the total protein is approximately 0.1% in the brain and liver, 1% in the heart and kidney, 4% in the muscle and lung, 6% in the colon, 20-40% in the skin, 25-35% in bones, and 40-50% in tendons of wild-type (CD1 and CB57BL/6) mice, consistent with previous reports. Mice consist of 37 mg of collagen and 265 mg of protein per g of body weight. To our surprise, we find that collagen is approximately 12% in females and 17% in males of the total protein content of entire wild-type (CD1 and CB57BL/6) mice. High-Performance Liquid Chromatography approaches confirmed a 10-12% collagen over total protein estimates for female mice. Collagen staining methods and extracellular matrix-enriched proteomics estimated 5-6% of collagens over the total protein extracted. Although collagen type I is the most abundant collagen, the most abundant proteins are albumin, hemoglobulin, histones, actin, serpina, and then collagen type I. Analyzing amino acid compositions of mice revealed glycine as the most abundant amino acid. Thus, we provide reference points for collagen, matrisome, protein, and amino acid composition of healthy wild-type mice that are important for tissue and biomaterial engineering and for the comparison of these factors in various disease models.

The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis

“…Further, collagens are the most abundant cargo of secretory output constituting about 12-17% of total mice protein and represents one of the most abundant proteins in the ECM deposition of liver fibrosis [80,81]. In cirrhotic livers, collagen content increases four to seven-fold as compared to normal liver, and its production is closely coupled to the IRE1-P4HB pathway, possibly as a mechanism to enhance the secretory capacity of a cell and to avoid proteotoxicity due to the accumulation of misfolded collagen in HSCs [82,83].…”

Endoplasmic reticulum exit sites are segregated for secretion based on cargo size

“…13 Clearly, these small vesicles cannot export bulky cargoes, like lipoprotein particles, collagens and other molecules, that compose the extracellular matrix. [14][15][16][17][18] Considering that collagens constitute 17 % of mammalian dry weight 19 , this is not a small problem.…”