Evidence for increased pyridinoline concentration in fibrotic tissues in diffuse systemic sclerosis

Abstract

Systemic sclerosis is a generalized disease characterized mainly by the accumulation of collagen in the skin and internal organs. The aim of our study was to determine the amount of collagen cross-link pyridinoline (Pyd) in a variety of fibrotic tissues (skin, fascia, endocardium, bladder) from an autopsy patient with diffuse systemic sclerosis, and to compare these with normal tissues from the same patient. Mean concentrations of Pyd in the fibrotic skin samples (66 mmol/mol collagen) were more than two-times greater than those in the uninvolved normal samples (27 mmol/mol collagen). The increase of Pyd in the endocardium, fascia, and bladder was also markedly higher (1.41 x, 1.26 x and 2.64 x higher than normal samples). The increased deposition of collagen in systemic sclerosis is accompanied by a significantly increased amount of Pyd in the collagen of fibrotic tissues.

Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon

“…Furthermore, the accumulated collagen in fibrotic lesions shows an increase in hydroxyallysine cross-link levels (Bailey et al, 1975;Brenner et al, 2000;Brickley-Parsons et al, 1981;Brinckmann et al, 1999Brinckmann et al, , 2001Di Donato et al, 1997;Gelberman et al, 1980;Istok et al, 2001;Last et al, 1990;Moriguchi and Fujimoto, 1979;Reiser and Last, 1987;Ricard-Blum et al, 1992, 1993Uzawa et al, 1998). The increased amount of these cross-links in fibrosis is the result of an overhydroxylation of the Lys residues within the telopeptides.…”

“…Interestingly, during the fibrotic process, a switch from the allysine route to the hydroxyallysine route occurs (Brinckmann et al, 1999) which results in the increased formation of pyridinoline cross-links derived from the hydroxyallysine route. This switch seems to be a general fibrotic phenomenon, as increased formation of hydroxyallysine cross-links (such as pyridinolines) has been found in various fibrotic tissues and organs, such as the skin (hypertrophic scars, keloid, systemic sclerosis (SSc) and lipodermatosclerosis; Bailey et al, 1975;Brinckmann et al, 1999Brinckmann et al, , 2001Istok et al, 2001;Moriguchi and Fujimoto, 1979;Ricard-Blum et al, 1993;Uzawa et al, 1998), the lung (infant/adult respiratory distress syndrome and interstitial lung disease; Last et al, 1990;Reiser and Last, 1987), the liver (parasitic, viral, and alcoholic cirrhosis; Brenner et al, 2000;Ricard-Blum et al, 1992, the kidney (glomerulosclerosis and interstitial fibrosis; Di Donato et al, 1997) and the palmar fascia (Dupuytren's disease: Brickley-Parsons et al, 1981;Gelberman et al, 1980). The observation that the increased formation of hydroxyallysine cross-links is related to the irreversible accumulation of collagen in fibrotic lesions suggests that collagen containing these kind of cross-links is more difficult to degrade, thereby contributing to the unwanted collagen accumulation (Bailey et al, 1975;Bailey and Light, 1985;Last et al, 1990;Ricard-Blum et al, 1992, 1993.…”

The molecular mechanism of photodynamic therapy to fibrosis: Regulation on the pyridinoline cross-link formation in collagen

“…The structure of pyridinoline is shown in Figure 3. The pyridinoline cross-linking of collagen was increased and became the major cross-linking in the process of fibrosis [35,36] , and the pyridinoline crosslink in tissue can be used as the diagnostic indicators for fibrosis [22,23] . Therefore, 392 nm fluorescence may be used as a probe for pyridinoline cross-link.…”

“…In the fibrotic process, the collagen is cross-linked mainly via the hydroxyallysinecross-links such as the pyridinolines. In fact, the level of pyridinoline has been used as a symbol to diagnose fibrosis clinically [20][21][22][23] . It was also reported that the pyridinoline cross-link in the fibrotic skin could be photo-degraded by psoralen under the ultraviolet light [24] , and PDT could kill the P. aeruginosa in cys-…”

Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: Implications for collagen cross-linking and treatment of fibrosis

“…In fibrotic disorders, which are characterised by an accumulation of collagen, an increase in hydroxyallysine cross-linking is observed (Bailey et al, 1975;Brenner et al, 2000;Istok et al, 2001;Last et al, 1990;Ricard-Blum et al, 1992). There are strong indications that these cross-links diminish the susceptibility of collagen to proteolytic degradation and in this way contribute to the unwanted collagen accumulation in fibrosis (Bailey et al, 1975;Bailey and Light, 1985;Last et al, 1990;Ricard-Blum et al, 1992, 1993.…”