{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:43:56Z","timestamp":1792147436165,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Proteinuria is a cardinal symptom of kidney disease, but common transient proteinurias may reflect a normal physiological response to distant tissue damage or infection. Here we observed that activation of Toll\u2010like receptor\u20104 (TLR4) using the selective agonist CRX572 induced three distinct functional effects in cultured podocytes. TLR4 activation evoked a reversible increase in albumin flux (\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>Alb<\/jats:sub>\n                    ) across a confluent layer of podocytes in 60\u2009m or less. At 24\u2009h matrix metalloproteinase\u2010dependent shedding of nephrin ectodomains was detected. Finally, apoptosis occurred after 72\u2009h. These effects were blocked by TAK242, a selective TLR4 antagonist. TLR4 activation engaged multiple intracellular transduction cascades. Activation of Erk was observed at 30\u2009m, increased reactive oxygen species (ROS) was seen at 60\u2009m and 24\u2009h, and activation of NF\u03baB was seen with 24\u2009h of TLR activation. The increase in\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>Alb<\/jats:sub>\n                    required increased ROS and activation of Erk. The subsequent nephrin ectodomain shedding also required Erk signaling but did not require increased cytosolic ROS or NF\u03baB activation. Finally, TLR4\u2010evoked apoptosis required both increased ROS and activation of NF\u03baB but did not require Erk activation. Innate immune signaling through TLR4 may alter glomerular function via parallel pleiotropic signaling cascades in podocytes.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71147","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:45:51Z","timestamp":1792143951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TLR4<\/scp>\n                    signaling cascades leading to increases in albumin permeability, nephrin ectodomain shedding, and apoptosis in\n                    <scp>MPC<\/scp>\n                    \u20105 podocytes"],"prefix":"10.14814","volume":"14","author":[{"given":"Eun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-104X","authenticated-orcid":false,"given":"Stuart E.","family":"Dryer","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston Texas USA"},{"name":"Department of Biomedical Sciences Tilman J. Fertitta Family College of Medicine, University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24461"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00153.2012"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007040395"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jrn.2007.10.031"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178716"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00109.2014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00442.2007"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184341"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)64128\u20104"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.04.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00038.2017"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20757"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17108"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.3.478"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004080679"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.03.008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00140.2008"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.70614"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39513"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400369R"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467\u2010016\u20103358\u20109"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00478.2012"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939992"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5508"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.07.013"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.20070404861"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010025\u201002149\u20104"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097985"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000531"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP088637"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1111"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20402"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1615\/critrevimmunol.v31.i5.20"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7962"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002291"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.06.056"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310760200"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2009.00297.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122399"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.263020"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094969"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(82)80287\u20104"}],"container-title":["Physiological 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