Increased airway smooth muscle (ASM) mass is believed to underlie the relatively fixed airway hyperresponsiveness (AHR) in asthma. Developments of therapeutic approaches to reverse airway remodeling are impeded by our lack of insight on the mechanisms behind the increase in mass of contractile ASM cells. Increased expression of laminin, an extracellular matrix protein, is associated with asthma. Our studies investigate the role of laminin-induced ASM survival signals in the development of increased ASM and AHR. Antagonizing laminin integrin binding using the laminin-selective competing peptide, YIGSR, and mimicking laminin with exogenous α2-chain laminin, we show that laminin is both necessary and sufficient to induce ASM cell survival, concomitant with the induction of ASM contractile phenotype. Using siRNA, we show that the laminin-binding integrin α7β1 mediates this process. Moreover, in laminin-211-deficient mice, allergen-induced AHR was not observed. Notably, ASM cells from asthmatic airways express a higher abundance of intracellular cell survival proteins, consistent with a role for reduced rates of cell apoptosis in development of ASM hyperplasia. Targeting the laminin-integrin α7β1 signaling pathway may offer new avenues for the development of therapies to reduce the increase in mass of contractile phenotype ASM cells that underlie AHR in asthma.
The utilization of urban underground space (UUS) offers an effective solution to urban problems but may also negatively affect urban development. Therefore, UUS development needs better concerted guidelines to coordinate various urban systems and the multiple components of the underground world. Sustainable Development Goals (SDGs), which should be viewed as important yardsticks for UUS development, do not explicitly mention urban underground space, although many of them are affected by both the positive and negative consequences of its development. To fill this gap, this review lays the foundations of relevant UUS concepts and uses exemplary cases to reveal that 11 out of 17 SDGs can be linked with UUS uses. These linkages also manifest that land administration, integrated planning, architectural design, and construction technology are critical dimensions for increasing the contributions of UUS to the realization of SDGs. To achieve multi-disciplinary synergies among these four critical dimensions, a collaborative approach framework based on spatial data infrastructure is required. Thus, this work provides academics and practitioners with a holistic view of sustainable UUS development.
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