Collagen and tissue turnover as a function of age: Implications for fibrosis

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• 作者：Morten A. Karsdal¹ ; ^&dagger ; ; ^{mk@nordicbioscience.com" class="auth_mail" title="E-mail the corresponding author} ; Federica Genovese¹ ; ^&dagger ; ; Emilie A. Madsen¹ ; Tina Manon-Jensen¹ ; Detlef Schuppan² ; ³
• 关键词：Collagen ; Age ; Tissue ; MMP ; Elastin ; Fibrosis ; Liver ; ccl4 ; Fibrogenesis ; Biomarkers ; Turnover ; Animal
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：64
• 期：1
• 页码：103-109
• 全文大小：872 K

文摘

The extracellular matrix (ECM) is the backbone of all tissues. It is a complex grid consisting of multiple structural proteins which each play a vital role for the function and maintenance of normal tissue function. In development and growth, tissue is being formed and elaborated (tissue modeling), while in adult life, tissues are being maintained and remodeled. These processes involve likely different mechanisms. During tissue modeling and remodeling, small fragments of proteins are released into the circulation, where they may be used as biomarkers for tissue turnover. The aim of the study was to investigate ECM turnover in rodents as a function of age.

Methods

Serum of rats of 1, 2, 3, 4, 5, 6, 10 and 12 months of age was profiled for 15 markers of ECM turnover, including: fragments of type I, II, III, IV, V and VI collagen formation (P1NP, P4NP-7S, Pro-C5, Pro-C6) and degradation (C1M, C2M, C2M-beta, C3M, C4M, C5M, C6M); biglycan (BGM) and elastin (ELM7) degradation; and the type I and II collagen telopeptides CTX-I and CTX-II.

Results

Type I and II collagen turnover was up to 93% and 97% downregulated in old (one year) compared to young (one month) old animals (m>pm> <0.0001), while type IV and V collagen and biglycan turnover was upregulated 2.5-, 2- and 2-fold, respectively (m>pm> <0.0001). Type III and VI collagen and elastin turnover was not influenced significantly by age.

Conclusions

ECM turnover rates were consistently different in young m>vs.m> old animals, up to 30 fold. This appears to be due to body growth, a different ECM composition and a higher regenerative capability of connective tissues in young m>vs.m> old animals. These changes have to be accounted for in translational science. Both in measuring serum levels of ECM biomarkers and in the development of therapies to speed up wound healing or inhibit fibrogenesis.