Expression of collagens type I and V in healing rat's tympanic membrane

Makuszewska, Maria; Bonda, Tomasz A.; Cieślińska, Magdalena; Bialuk, Izabela; Winnicka, Maria M.; Skotnicka, Bożena; Hassmann‐Poznańska, Elżbieta

doi:10.1016/j.ijporl.2018.12.020

Cited by 8 publications

(7 citation statements)

References 18 publications

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“…From a molecular point of view, most collagen fibril consist of a large number of type I collagen and a very small number (∼2%) of type V collagen. Although type V collagen only occupies small portion of collagens in all tissues, it is crucial for collagen fibril nucleation, regarded as collagen fibrillogenesis (Connizzo et al, 2015; Makuszewska et al, 2019). Mouse model results indicate that the deficiency or abnormality of type V collagen leads to a lack of fibril formation in mouse embryonic tissue and even death in the stage of early embryos (Wenstrup et al, 2004; Connizzo et al, 2015), which is similar to the phenotypes in human OI type II (perinatal lethal type).…”

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease

et al. 2019

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Osteogenesis imperfecta (OI), mainly caused by structural abnormalities of type I collagen, is a hereditary rare disease characterized by increased bone fragility and reduced bone mass. Clinical manifestations of OI mostly include multiple repeated bone fractures, thin skin, blue sclera, hearing loss, cardiovascular and pulmonary system abnormalities, triangular face, dentinogenesis imperfecta (DI), and walking with assistance. Currently, 20 causative genes with 18 subtypes have been identified for OI, of them, variations in COL1A1 and COL1A2 have been demonstrated to be major causative factors to OI. However, the complexity of the bone formation process indicates that there are potential new pathogenic genes associated with OI. To comprehensively explore the underlying mechanism of OI, we conducted association analysis between genotypes and phenotypes of OI diseases and found that mutations in COL1A1 and COL1A2 contributed to a large proportion of the disease phenotypes. We categorized the clinical phenotypes and the genotypes based on the variation types for those 155 OI patients collected from literature, and association study revealed that three phenotypes (bone deformity, DI, walking with assistance) were enriched in two variation types (the Gly-substitution missense and groups of frameshift, nonsense, and splicing variations). We also identified four novel variations (c.G3290A (p.G1097D), c.G3289C (p.G1097R), c.G3289A (p.G1097S), c.G3281A (p.G1094D)) in gene COL1A1 and two novel variations (c.G2332T (p.G778C), c.G2341T (p.G781C)) in gene COL1A2, which could potentially contribute to the disease. In addition, we identified several new potential pathogenic genes (ADAMTS2, COL5A2, COL8A1) based on the integration of protein–protein interaction and pathway enrichment analysis. Our study provides new insights into the association between genotypes and phenotypes of OI and novel information for dissecting the underlying mechanism of the disease.

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Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease

et al. 2019

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“…In fact, by one week, perforations were often difficult to locate because the healed perforation areas appeared to have fibrous regrowth, resembling the surrounding un-perforated membrane. The healing of the RWM appears remarkably similar to the healing process described in the tympanic membrane, which also begins with epithelial migration followed by possible fibrous regrowth (18,(25)(26)(27). Future investigation into cell signaling and growth factors would help to elucidate the long-term healing of the RWM.…”

Section: Discussionmentioning

confidence: 54%

Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane

Arteaga

Aksit³

et al. 2020

Otology &Amp; Neurotology

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Hypothesis: Microneedles can create microperforations in the round window membrane (RWM) without causing anatomic or physiologic damage.Background: Reliable delivery of agents into the inner ear for therapeutic and diagnostic purposes remains a challenge. Our novel approach employs microneedles to facilitate intracochlear access via the RWM. This study investigates the anatomical and functional consequences of microneedle perforations in guinea pig RWMs in vivo.Methods: Single 3D-printed, 100 μm diameter microneedles were used to perforate the guinea pig RWM via the postauricular sulcus. Hearing was assessed both before and after microneedle perforation using compound action potential and distortion product otoacoustic emissions. Confocal microscopy was used ex vivo to examine harvested RWMs, measuring the size, shape, and location of perforations and documenting healing at 0 hours (n = 7), 24 hours (n = 6), 48 hours (n = 6), and 1 week (n = 6).Results: Microneedles create precise and accurate perforations measuring 93.1 ± 29.0 μm by 34.5 ± 16.8 μm and produce a high frequency threshold shift that disappears after 24 hours. Examination of perforations over time demonstrates healing progression over 24-48 hours and complete perforation closure by one week. Conclusion:Microneedles can create a temporary microperforation in the RWM without causing significant anatomic or physiologic dysfunction. Microneedles have the potential to mediate safe and effective intracochlear access for diagnosis and treatment of inner ear disease.

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“…No animals were excluded from the study due to middle ear inflammatory process before or in the course of the experiment. TM perforations were performed according to the method described in our previous publications [ 6 , 7 , 24 , 25 ]. Perforations engulfing the whole upper anterior quadrant of TM in both ears were performed under an operating microscope with a sterile, sharp point, microsurgical needle.…”

Section: Methodsmentioning

confidence: 99%

“…Formalin-fixed, paraffin-embedded tissue blocks were serially sectioned into 5-µm slices and stained with hematoxylin and eosin (H&E) for basic histological assessment or used for immunofluorescence staining showing tissue distribution of proteins sought. The sections for immunofluorescence were processed and blocked as previously described [ 25 ]. The primary antibodies against tPA (bs-1545R, Bioss Antibodies, RRID: AB_10855981), uPA (FNab09267, Wuhan Fine Biotech Co.), uPAR (bs-1927R, Bioss Antibodies, RRID:AB_10856881), and PAI-1 (SERPINE1, bs-6562R, Bioss Antibodies, RRID: AB_11114126) were applied at 1:100 dilution in PBS for 90 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

Makuszewska

Cieślińska

Winnicka

et al. 2023

JARO

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The significance of plasminogen activation during the tympanic membrane (TM) healing is known mainly from studies performed on knock-out mice. In the previous study, we reported activation of genes coding proteins of plasminogen activation and inhibition system in rat’s TM perforation healing. The aim of the present study was the evaluation of protein products expressed by these genes and their tissue distribution using Western blotting and immunofluorescent method, respectively, during 10-day observation period after injury. Otomicroscopical and histological evaluation were employed to assess the healing process. The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) were significantly upregulated in the proliferation phase, with subsequent gradual attenuation during remodeling phase of healing process, when keratinocyte migration was weakening. The expression of plasminogen activator inhibitor type 1 (PAI-1) also showed the highest levels during the proliferation phase. The increase of tissue plasminogen activator (tPA) expression was observed during the whole observation period, with the highest activity during the remodeling phase. Immunofluorescence of these proteins was present mainly in migrating epithelium. Our study found that plasminogen activation (uPA, uPAR, tPA) and inhibitory (PAI-1) molecules form a well-structured regulatory system of the epithelial migration that is critical to the healing of TM after its perforation.

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Expression of collagens type I and V in healing rat's tympanic membrane

Cited by 8 publications

References 18 publications

Genotype–Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease

Genotype–Phenotype Association Analysis Reveals New Pathogenic Factors for Osteogenesis Imperfecta Disease

Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

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