Podocytes are epithelial cells adhering glomerular capillaries, which regulate the integrity of glomerular filtration barrier. Irreversible podocyte injury induces glomerular inflammation and causes chronic renal diseases. Kcnq1ot1, a long non-coding RNA (lncRNA), participates in the pathogenesis of diabetic retinopathy and cardiomyopathy. However, its function in podocyte injury is elusive. Pyroptosis of murine podocyte MPC5 was triggered by sublytic complement C5b-9 (sC5b-9) for subsequent in vitro functional and mechanistic investigation. Gain/Loss-of-function analysis was conducted to examine the functional role of Kcnq1ot1 in podocyte pyroptosis. Meanwhile, the molecular mechanism of Kcnq1ot1's effect on podocyte injury was explored by identifying downstream molecules and their intermediate interactions. Kcnq1ot1 was upregulated in sC5b-9-induced podocytes, and silencing Kcnq1ot1 could inhibit sC5b-9's effect on podocyte pyroptosis. We also identified the interaction between Kcnq1ot1 and miR-486a-3p, through which Kcnq1ot1 mediated miR-486a-3p inhibition by sC5b-9. Furthermore, miR-486a-3p reduced the transcriptional activity of NLRP3, while the overexpression of NLRP3 enhanced sC5b-9's effect on podocyte pyroptosis through activating NLRP3 inflammasome. sC5b-9 induces pyroptosis in podocytes through modulating the Kcnq1ot1/miR-486a-3p/NLRP3 regulatory axis, and these uncovered key molecules might facilitate podocyte-targeted treatment for renal inflammatory diseases.
Affected by global changes, extreme weather has become more frequent in recent years, which has had a huge impact on the urban environment. As a collection of human civilization achievements, cities have created vitality and prosperity, but with the advancement of urbanization, huge risks have emerged in the urban environment. The resilience of a city is like the immune system of a city. It is an indispensable part of urban construction. It can enable the urban environment to effectively cope with, alleviate, and eliminate risks to ensure the healthy development of the city. Starting from the definition of resilient city, this article discusses the assessment methods of resilient cities, the current construction of resilient cities, the high temperature characteristics of Jing’an District, and the spatial characteristics of Jing’an District.
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