Basement membrane components in healing rabbit corneal epithelial wounds: immunofluorescence and ultrastructural studies.

The nature of the substrate that supports epithelial migration in vivo is of interest, particularly with respect to mechanisms of wound healing. Immunofluorescence and electron microscopy were used to search for common substrate components in prototype rabbit corneal wounds: epithelial scrape wounds, in which the corneal or conjunctival epithelium migrated over the denuded lamina densa of the corneal basement membrane (CBM), and superficial keratectomy, in which the corneal epithelium migrated over a bare stroma without CBM. The corneal epithelium moved rapidly over the CBM or stroma to cover the defect within 2-3 d, whereas the conjunctival epithelium required 1-2 wk. In all wounds, fibronectin and fibrin/fibrinogen were deposited onto the bare surface within 8 h after wounding and persisted under the migrating epithelium until migration was complete. Bullous pemphigoid antigen (BPA), a normal component of the CBM, was removed with the epithelium upon scrape wounding and reappeared in the CBM after migration was completed. In contrast, the conjunctival epithelium had a continuous subepithelial band of BPA out to the migrating tip. Laminin, also a normal component of the CBM, was not removed in the scrape wounds, indicating that the region of least resistance to shear stress was between the BPA and laminin layers. Laminin was removed by superficial keratectomy and was not detectable under the leading edge of the migrating cells. Laminin and BPA were restored in the CBM by 2-4 wk. Type IV collagen could not be detected in normal CBM, but was conspicuously present in conjunctival basement membrane and in blood vessels. Focal bands of type IV collagen did appear in the newly synthesized CBM 2-4 wk after keratectomy. These results argue that BPA, laminin, and type IV collagen are not essential for the migration of corneal epithelium during wound healing and support the hypothesis that fibronectin and fibrin/fibrinogen are the common, perhaps the essential, components of the provisional matrix that serves as a substrate until the permanent attachment components are regenerated.

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Type IV Collagen in the Basement Membrane of the Corneal Epithelium after Alkali Burns in Guinea Pigs

Ophthalmic Research ◽

10.1159/000267645 ◽

1995 ◽

Vol 27 (3) ◽

pp. 129-135 ◽

Cited By ~ 3

Author(s):

Shizuya Saika ◽

Sakae Kobata ◽

Natsuko Hashizume ◽

Osamu Yamanaka ◽

Yuka Okada ◽

...

Keyword(s):

Basement Membrane ◽

Corneal Epithelium ◽

Guinea Pigs ◽

Type Iv Collagen ◽

Type Iv

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Abnormal Deposition of Laminin and Type IV Collagen at Corneal Epithelial Basement Membrane During Wound Healing in Diabetic Rats

Japanese Journal of Ophthalmology ◽

10.1016/s0021-5155(99)00095-7 ◽

1999 ◽

Vol 43 (5) ◽

pp. 343-347 ◽

Cited By ~ 18

Author(s):

N Sato

Keyword(s):

Wound Healing ◽

Basement Membrane ◽

Type Iv Collagen ◽

Diabetic Rats ◽

Corneal Epithelial ◽

Epithelial Basement Membrane ◽

Type Iv ◽

Epithelial Basement

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Structure, compositon and function of the dermal-epidermal junction: Relevance in cutaneous disease and diagnosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100156328 ◽

1989 ◽

Vol 47 ◽

pp. 868-869

Author(s):

K. A. Holbrook

Keyword(s):

Basement Membrane ◽

Epidermolysis Bullosa ◽

Normal Skin ◽

Lamina Densa ◽

Inherited Disorders ◽

Ultrastructural Studies ◽

Type Iv ◽

Type Vii Collagen ◽

Attachment Structures ◽

Matrix Components

The dermal-epidermal junction (DEJ), or basement membrane rone, is the boundary between the epithelial and mesenchymal compartments of the skin; epidermal and fibroblastic cells in these two regions collaborate to synthesire its components. Ultrastructural studies (TEM and SEM) have defined a series of planes or layers (basal epidermal, lamina lucida, lamina densa, sublamina densa) and the morphology and density of attachment structures (hemidesmosomes, anchoring filaments, anchoring fibrils and anchoring plaques) in this region of normal skin. Change in structure of the DEJ provides information about the history of the tissue; reduplication of the lamina densa, for example, indicates a site of cell detachment or migration, or remodelling that accompanies repair of focal damage. In normal skin the structure of the DEJ is stable; in pathologic conditions it can be compromised by the congenital absence of certain structures or antigens (e.g., in the inherited disorders, epidermolysis bullosa [EB]) or by enzymatic degradation (e.g., in tumor invasion). Dissolution of the DEJ can also occur normally during the formation of epidermal appendages (e.g., hair follicles) and as melanocytes and Langerhans cells migrate into the epidermis during development.Biochemical and immunohisto/cytochemical studies have identified more than 20 molecules at the DEJ. These include well known matrix molecules (e.g., types IV and V collagen, laminin and fibronectin) and skin-specific antigens. The latter have been identified by autoantibodies or specific polyclonal or monoclonal antibodies raised against the skin, cultured cells and other epithelia. Some of the molecules of the DEJ are are present in basement membrane zones of many epithelia and thus are considered ubiquitous components (type IV, V, laminin, fibronectin, nidogen, entactin, HSPG, LDA-1, CSP [3B3]). All of them (that have been investigated in developing skin) appear ontogenetically as early as human embryonic tissue can be obtained and their expression is typically normal in patients with EB. The known properties of many of these molecules (particularly the matrix components) suggest functions they might impart to the DEJ: support of an epithelium (type IV collagen), regulation of permeability (heparan sulfate proteoglycan) or facilitation of cell attachment (fibronectin) and movement (laminin). Another group of matrix components and antigens of the DEJ includes molecules that are skin-specific or characteristic of stratified squamous epithelia (type VII collagen=LH 7:2 antigen, bullous pemphigoid antigen, AA3, GB3, KF-1,19-DEJ-1, epidermolysis bullosa acquisita antigen [EBA], AF-1 and AF-2, cicatricial pemphigoid antigen [CPA]) . These molecules are expressed in the DEJ later in development than the first group of molecules, in conjunction with the morphologic appearance of the structure they represent. Their appearance is also coordinated with specific developmental events (e.g., epidermal stratification) and the expression of molecules of differentiation in the epidermis and dermis. One or more of them is typically absent or reduced in expression in the skin of patients with heritable disorders affecting this region. There is no apparent correlation between the location of molecules in the DEJ and the stability of their expression.

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Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis

Cell Death and Disease ◽

10.1038/s41419-021-03443-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Yuexin Wu ◽

Yuyan Cao ◽

Keren Xu ◽

Yue Zhu ◽

Yuemei Qiao ◽

...

Keyword(s):

Liver Cirrhosis ◽

Basement Membrane ◽

Type Iv Collagen ◽

Patient Survival ◽

Early Stage ◽

Ecm Remodeling ◽

Type Iv ◽

Ecm Proteins ◽

Stage Disease ◽

Cirrhotic Patients

AbstractLiver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen α5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen α5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.

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