Increased Skin Collagen Extractability and Proportions of Collagen Type III Are Not Normalized after 6 Months Healing of Human Excisional Wounds

Abstract

In an attempt to identify potential staging markers of effective healing, changes in connective tissue properties were measured in a human skin excisional wound healing model in which tissue was re-excised at intervals up to 6 months after injury. The proportion of collagen III relative to collagen I increased significantly (p<0.001) up to 6 weeks after initial injury and remained elevated up to 6 months, at which time the proportion of collagen III was 70% above baseline values. Extractability of biopsy tissue collagen by pepsin increased significantly throughout the study (baseline, 32.8+/-6.8%; 6 months, 89.1+/-8.9%), with inverse changes in the mature skin cross-link, histidinohydroxylysinonorleucine (baseline, 1.18+/-0.11 mol/mol collagen; 6 months, 0.27+/-0.09 mol/mol collagen). Pyridinoline content increased over the period of the study, although remaining at relatively low concentrations (baseline, 0.037+/-0.011; 6 months, 0.063+/-0.014 mol/mol collagen), and the pyridinoline/deoxypyridinoline ratio was significantly higher (baseline, 3.5+/-0.6; 6 months, 10.3+/-2.2). Elastin content, measured as desmosine cross-links, decreased significantly in the first 3 weeks and continued to decline over the period of study. Overall, the data suggest that remodeling of the wound tissue continues at least up to 6 months after injury. The close inverse correlation between histidinohydroxylysinonorleucine concentrations and extractability by pepsin (r2=0.89, p<0.0001) suggests a causal relationship, consistent with the likely effects of a substantial network of mature, inter-helical bonds in collagen.

Effect of pERK2 on extracellular matrix turnover of the fibrotic joint capsule in a post-traumatic joint contracture model

“…In contrast to total collagen and collagen I, staining for collagen III was more intense in the control capsules, which is in agreement with the results of the study by Matsumoto et al (20). These results demonstrate a mechanism of contracture tissue formation that differs from that of wound healing, with increased levels of collagen type III (21,22). Similar to total collagen and collagen I, the levels of MMP-13 and MMP-1 were increased in the capsule of the ORC group compared with the CON group in the present study.…”

Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-β

“…Especially, the composition of the extracellular matrix in wound healing and sclerosis shares many features of an embryo-fetal matrix. This 'embryonic reprogramming' was shown for collagen and its modification, 12,14,15,17,32,33 for adhesive glycoproteins, [34][35][36][37] and for matricellular proteins. 38 The data presented here show that the microfibrillar protein fibrillin-2, which is a typical component of embryonic skin but only scarcely expressed at the dermoepidermal junction in adult skin, is strongly re-expressed throughout the The isodesmosine (Ide) and desmosine (Des) content of collagenase-digested and hydrolyzed skin specimens was measured by amino acid analysis.…”

“…In fact, our data show a marked decrease of the mature elastin content in sclerotic skin from LDS patients, correlating with other published data for wound healing and scleroderma which show the presence of fibrillin-containing microfibrils without amorphous elastin in the lower dermis. 15,46,47 The decrease in the mature elastin content was not caused by reduced lysyl oxidase gene expression, which was in fact three-fold increased as compared with normal skin. Changes in the concentration of elastin crosslinks may be caused by an altered gene expression level of elastin, a variation of elastin splice variants or changes in the degree of prolyl hydroxylation of elastin.…”

“…[12][13][14] Furthermore, collagen cross-links in healing skin wounds and in sclerotic skin of hypertrophic scars, lipodermatosclerosis (LDS) and scleroderma are characterized by a shift from lysine-aldehyde derived cross-links primarily observed in adult skin to hydroxylysine-aldehyde derived cross-links characteristic for fetal skin. [15][16][17] Also, for several non-collagenous matrix proteins an increase of embryo-fetal proteins was reported in wound healing and sclerosis: The splice variant EDA of fibronectin, a 440 kDa adhesive matrix glycoprotein characterized by an additional type III repeat between repeats 11 and 12, is expressed in the developing embryo, but is barely detectable in adult skin. EDA was also found in wound healing and sclerosis and together with TGF-b is thought to be important for the generation of myofibroblasts.…”

Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice

“…Changes in the solubility characteristics of collagen depend on the number of covalent cross-links between collagen triple helices which are required for the formation of stable collagen fibrils (Robins et al 2003). Previous studies in humans confirm increased solubility of collagen in the presence of acetic acid and pepsin during cervical ripening (Granstrom et al 1989).…”