SELENOT, a Key Membrane-Bound Selenoprotein, Mediates Selenium’s Protection Against Lead-Induced Renal Aging in Chickens by Modulating Inflammation and Autophagy

Lead (Pb) pollution is a global public health issue, yet the mechanisms underlying Pb-induced kidney aging remain poorly understood. Selenium (Se), an essential trace element critical for kidney health, primarily exerts its physiological roles via selenoproteins; among them, membrane-bound selenoproteins strategically localized at the endoplasmic reticulum and plasma membrane, have emerged as potential molecular links in Se-mediated protection. In this study, Hyline chicken models (treated with 350.00 mg/L Pb or/and 1.00 mg/kg Se) and HK-2 cell models (treated with 200 μM Pb or/and 2.5 μM Se) were established to investigate the protective mechanism of Se to Pb poisoning in kidneys, with emphasis on membrane-bound selenoproteins and kidney aging. Results showed that Pb significantly decreased (p < 0.05) membrane-bound selenoproteins and induced kidney aging. Inflammation and autophagy were involved, as Pb significantly increased (p < 0.05) pro-inflammatory cytokines interleukin-4 (IL-4) and interleukin-12β (IL-12β), and autophagy-related genes autophagy related 5 (ATG5), BCL2 interacting coiled coil protein 1 (Beclin 1), and microtubule-associated protein 1A/1B-light chain 3 (LC3-II) while significantly suppressing (p < 0.05) interleukin-2 (IL-2) and mammalian target of rapamycin (mTOR). Se had a relieving effect on it, as evidenced by significantly reversing (p < 0.05) the changes in the above indicators. Interestingly, Selenoprotein T (SELENOT), as a hub membrane-bound selenoprotein, is sensitive to Pb poisoning (Pb exposure decreased SELENOT mRNA expression to 56%, 34%, and 19% of the control levels at 30, 60, and 90 days, respectively). Knockdown of SELENOT aggravated Pb-induced inflammation, autophagy, and cellular senescence, meaning that SELENOT protected against kidney aging via suppressing inflammation and autophagy under Pb stress. These findings establish membrane-bound selenoproteins as essential molecular hubs that orchestrate inflammation resolution and autophagy in Se’s antagonism against Pb-induced kidney aging, highlighting promising therapeutic targets for nephropathy.