Deciphering the Protective Role of HIF-1α Downregulation on HIBD through the MALAT1/miR-140-5p/TGFBR1/NF-κB Signaling Pathway

Hypoxic-ischemic brain damage (HIBD) in neonates is a substantial cause of mortality and neurodevelopmental impairment, with the exact molecular mechanisms still being elucidated. The involvement of HIF-1α, MALAT1, miR-140-5p, TGFBR1, and the NF-κB signaling pathway in such injury cascades is of increasing research interest due to their pivotal roles in cellular and pathological processes. This study aimed to explore how HIF-1α regulates the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis to participate in the molecular mechanisms of HIBD in neonatal rats. Utilizing bioinformatic analyses and a suite of experimental approaches, the study delineated interactions and regulatory relationships among the molecules. Knockdown of HIF-1α was shown to mitigate brain tissue damage in a neonatal HIBD rat model through the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis, revealing a protective effect achieved by inhibiting hippocampal neuron apoptosis and potentially guiding the way toward therapeutic interventions in HIBD. This study implicates the HIF-1α mediated regulation of the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis in the pathological development of HIBD, offering insights into novel potential interventional strategies.