Age-dependent regulation of cell-mediated collagen turnover
| Autor: | Ritwik Datta, Michael J Podolsky, Sarah L. Dallas, Claude Jourdan Le Saux, Paul J. Wolters, Steven K. Huang, Christopher D Yang, Kamran Atabai, Carlos Lizama Valenzuela, Stephen L. Nishimura |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging Pulmonology Transcription Genetic Knockout 1.1 Normal biological development and functioning Endocytic cycle Kruppel-Like Transcription Factors Receptors Cell Surface Biology Extracellular matrix Mice 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine Genetic Downregulation and upregulation Underpinning research Fibrosis Receptors Genetics medicine 2.1 Biological and endogenous factors Animals Aetiology Receptor Transcription factor Mice Knockout Membrane Glycoproteins General Medicine medicine.disease Extracellular Matrix Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Cell Surface Proteolysis Collagen Transcription Collagens Mannose receptor Research Article |
| Zdroj: | JCI Insight JCI insight, vol 5, iss 10 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.137519 |
| Popis: | Although aging represents the most important epidemiologic risk factor for fibrotic disease, the reasons for this are incompletely understood. Excess collagen deposition in tissues is the sine qua non of tissue fibrosis and can be viewed as an imbalance between collagen production and collagen degradation. Yet we still lack a detailed understanding of the changes that take place during development, maturation, and aging in extracellular matrix (ECM) dynamics. Resolution of fibrosis is impaired in aging, and this impairment may explain why age is the most important risk factor for fibrotic diseases, such as idiopathic pulmonary fibrosis. However, ECM dynamics and impaired resolution of fibrosis in aging remain understudied. Here we show that cell-mediated collagen uptake and degradation are diminished in aged animals and this finding correlates with downregulation of the collagen endocytic receptor mannose receptor, C-type 2 (Mrc2). We identify myeloid zinc finger-1 as a potentially novel transcriptional regulator of Mrc2, and both this transcription factor and Mrc2 are downregulated in multiple tissues and organisms in an age-dependent manner. Thus, cell-mediated degradation of collagen is an essential process that promotes resolution of fibrosis, and impairment in this process contributes to age-related fibrosis. |
| Databáze: | OpenAIRE |
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