Type IV collagen alpha chains of the basement membrane in the rat bronchioalveolar transitional segment

Hinenoya, Noriko; Naito, Ichiro; Momota, Ryusuke; Sado, Yoshikazu; Kumagishi, Kanae; Ninomiya, Yoshifumi; Ohtsuka, Aiji

doi:10.1679/aohc.71.185

Cited by 10 publications

(8 citation statements)

References 22 publications

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“…Bronchiolar and alveolar epithelium also rely on collagen IV for adhesion, differentiation, and migration [23]. To quantify this basement membrane component, we evaluated α2 and α5 chains of collagen IV.…”

Section: Resultsmentioning

confidence: 99%

Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices

et al. 2016

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Extracellular matrix is a key component of many products in regenerative medicine. Multiple regenerative medicine products currently in the clinic are comprised of human or xenogeneic extracellular matrix. In addition, whole-organ regeneration exploits decellularized native organs as scaffolds for organotypic cell culture. However, precise understanding of the constituents of such extracellular matrix-based implants and scaffolds has sorely lagged behind their use. We present here an advanced protein extraction method using known quantities of proteotypic 13C-labeled peptides to quantify matrix proteins in native and decellularized lung tissues. Using quantitative proteomics that produce picomole-level measurements of a large number of matrix proteins, we show that a mild decellularization technique (“Triton/SDC”) results in near-native retention of laminins, proteoglycans, and other basement membrane and ECM-associated proteins. Retention of these biologically important glycoproteins and proteoglycans is quantified to be up to 27-fold higher in gently-decellularized lung scaffolds compared to scaffolds generated using a previously published decellularization regimen. Cells seeded onto this new decellularized matrix also proliferate robustly, showing positive staining for proliferating cell nuclear antigen (PCNA). The high fidelity of the gently decellularized scaffold as compared to the original lung extracellular matrix represents an important step forward in the ultimate recapitulation of whole organs using tissue-engineering techniques. This method of ECM and scaffold protein analysis allows for better understanding, and ultimately quality control, of matrices that are used for tissue engineering and human implantation. These results should advance regenerative medicine in general, and whole organ regeneration in particular.

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Section: Resultsmentioning

confidence: 99%

Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices

et al. 2016

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“…Although these scaffolds provide anatomic access to the airway and vascular compartments, one key challenge will be delivery of mesenchymal populations to the interstitium and particularly the delicate septa. Regionally specific mesenchymal populations, coupled with distinct extracellular matrix cues (Hinenoya et al, 2008; Sannes, 1984) may significantly enhance the outcomes of epithelial repopulation of decellularized matrices. However, the complexity of human lung will make this a daunting task for many years to come.…”

Section: Bioengineering Lung Tissuementioning

confidence: 99%

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Hogan¹,

Barkauskas²,

et al. 2014

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Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the mechanisms driving lung development and differentiation. However, there is still much to learn about the ability of the adult respiratory system to undergo repair and to replace cells lost in response to injury and disease. This review highlights the multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair.

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“…Tumour endothelial cells are abnormal [48,49], compared with non-diseased cells, and thus their response to lamstatin and CP17 may be different. The absence or decreased levels of histochemical detection for members of the Col IV family, especially Col IV a5 as we have reported here in LAM, are associated with higher levels of invasion in breast, prostate, bronchoalveolar and colorectal cancer [12,13,[50][51][52]. In addition, increased lymphangiogenesis is commonly found in those cancers (explicitly breast and prostate) and results in lymph node metastasis and invasion [14,[53][54][55][56].…”

Section: Discussionmentioning

confidence: 69%

Lamstatin – a novel inhibitor of lymphangiogenesis derived from collagen IV

Weckmann

Moir

Heckman

et al. 2012

J Cellular Molecular Medi

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The lymphatic system is essential for the maintenance of tissue homeostasis and immunity. Its dysfunction in disease (such as lymphangioleiomyomatosis) can lead to chylous effusions, oedema or dissemination of malignant cells. Collagen IV has six a chains, of which some of the non-collagenous-1 domains have endogenous anti-angiogenic properties, however, little is known about specific endogenous anti-lymphangiogenic characteristics. In this study we sought to investigate the expression levels of collagen IV non-collagenous-1 domains in lung tissue of patients with and without lymphangioleiomyomatosis to explore the hypothesis that a member of the collagen IV family, specifically the non-collagenous domain-1 of a5, which we named lamstatin, has anti-lymphangiogenic properties. Levels of lamstatin detected by immunohistochemistry were decreased in lungs of lymphangioleiomyomatosis patients. We produced recombinant lamstatin in an E.coli expression system and synthesized a 17-amino acid peptide from a theoretically identified, active region (CP17) and tested their effects in vitro and in vivo. Recombinant lamstatin and CP17 inhibited proliferation, migration and cord formation of human microvascular lung lymphatic endothelial cells, in vitro. Furthermore, lamstatin and CP17 decreased complexity and dysplasia of the tumour-associated lymphatic network in a lung adenocarcinoma xenograft mouse model. In this study we identified a novel, direct inhibitor of lymphangiogenesis, derived from collagen IV. This may prove useful for exploring new avenues of treatment for lymphangioleiomyomatosis and metastasis via the lymphatic system in general.

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Type IV collagen alpha chains of the basement membrane in the rat bronchioalveolar transitional segment

Cited by 10 publications

References 22 publications

Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices

Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices

Repair and Regeneration of the Respiratory System: Complexity, Plasticity, and Mechanisms of Lung Stem Cell Function

Lamstatin – a novel inhibitor of lymphangiogenesis derived from collagen IV

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