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Mechanical Signaling in the Urinary Bladder
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Aruna Ramachandran, Ramaswamy Krishnan, Rosalyn M. Adam
Although alterations in production of ECM proteins following bladder wall distension have been well documented, the molecular events underlying changes in ECM protein expression have not been fully elucidated. The immediate early gene Cyr61/CCN1 encodes a secreted, cysteine-rich, heparin-binding protein and functions as an ECM-associated signaling molecule. Cyr61 was shown to be induced in BSMC following cyclic stretch-relaxation, in a protein kinase C-, ROCK-, and PI3K/Akt-dependent manner [100]. Cyr61 and another immediate early gene product, connective tissue growth factor (CTGF/CCN2), also identified as mechanosensitive in BSMC [101], were found to be induced in the detrusor smooth muscle following PBOO in rats, with expression sustained for the duration of obstruction [102]. Among their various diverse functions, Cyr61 and CTGF are key regulators of wound healing and regulate the expression of various matrix-associated, angiogenic, and ECM-remodeling proteins such as MMPs, TIMPs, VEGF, and integrins [103,104].
Polymeric Gene Delivery Carriers for Pulmonary Diseases
Published in Severian Dumitriu, Valentin Popa, Polymeric Biomaterials, 2020
Xiang Gao, Regis R. Vollmer, Song Li
Suppressing inflammatory aspect of IPF by shifting Th1/Th2 imbalance in the lung with Th1 cytokines, such as IFN-γ, represents another potential approach to treat this disease. Alveolar macrophages from patients with IPF are known to be defective in IFN-γ production. Systemic administrations of Th1 cytokines have been shown to prevent lung fibrosis induced by bleomycin in animal models (Gurujeyalakshmi and Giri, 1995). An added benefit with IFN-γ treatment is the suppression of expression of cytokines known to induce proliferation of fibroblasts, such as TGF-β and connective tissue growth factor (CTGF). Preliminary results from a small-sized clinical trial of 18 IPF patients treated with long-acting IFN-γ-1b and glucosteriods showed improved lung volumes and gas exchange parameters, as well as lowered TGF-β and CTGF mRNA transcripts (Ziesche et al., 1999). However, a subsequent double-blind, placebo-controlled trial involving s.c. administration of IFN-γ-1b in 330 IPF patients has not been able to confirm the initial observations in terms of both molecular changes (Strieter et al., 2004) and clinical benefits (Raghu et al., 2004). It remains to be tested if locally expressed IFN-γ through less-toxic gene transfer approaches would have any therapeutic values in IPF.
Collagen of porcine auricle has unique biochemical and biophysical characteristics
Published in Soft Materials, 2019
Kenji Ishi, Hiroko Hoshi, Mina Takahashi, Koji Kitagawa, Masataka Hoshi, Norihiro Kawaguchi
It has been reported that auricular cartilage has unique potential in stem cell research (6,7). Human auricular perichondrium harbors a unique cell population that consists of cartilage stem and progenitor cells (7–9). The perichondrium, which surrounds the cartilage, contains progenitor cells capable of differentiating into chondroblasts. The progenitor cells within the perichindrium proliferate faster than mature chondrocytes and are able to differentiate into other mesenchymal tissues under defined conditions. Additionally, the connective tissue growth factor (CTGF) is a well-known fibroblast mitogen and angiogenic factor. Strong and persistent CTGF gene expression was particularly prominent in the mesenchyme of the cardiovascular system (aorta, auricular tissue, renal glomeruli). In the adult mouse, CTGF is involved in wound healing, as well as fibrotic and vascular disease (39). The reason why PAC-A promotes cell proliferation is not clear, but the fibrillogenesis and viscoelasticity of PAC-A may be related to functions such as those of perichondrocyte matrix.