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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1540639

High Mobility Group Box 1 (HMGB1) Mediates Nicotine-Induced Podocyte Injury

Provisionally accepted
Sayantap Datta Sayantap Datta 1Mohammad Atiqur Rahman Mohammad Atiqur Rahman 1Saisudha Koka Saisudha Koka 2Krishna M Boini Krishna M Boini 1*
  • 1 University of Houston, Houston, United States
  • 2 Texas A&M University, Kingsville, United States

The final, formatted version of the article will be published soon.

    Cigarette smoking is a well-established risk factor for renal dysfunction. Smoking associated with renal damage bears distinct physiological correlations in conditions such as diabetic nephropathy and obesity-induced glomerulopathy. However, the cellular and molecular basis of such an association remains poorly understood. High mobility group box 1(HMGB1) is a highly conserved non-histone chromatin associated protein that largely contributes to the pathogenesis of chronic inflammatory and autoimmune diseases such as sepsis, atherosclerosis, and chronic kidney diseases. Hence, the present study tested whether HMGB1 contributes to nicotine-induced podocyte injury. Biochemical analysis showed that nicotine treatment significantly increased the HMGB1 expression and release compared to vehicle treated podocytes. However, prior treatment with glycyrrhizin (Gly), a HMGB1 binder, abolished the nicotine-induced HMGB1 expression and release in podocytes.Furthermore, immunofluorescent analysis showed that nicotine treatment significantly decreased the expression of podocyte functional proteins-podocin and nephrin as compared to control cells. However, prior treatment with Gly attenuated the nicotine-induced nephrin and podocin reduction. In addition, nicotine treatment significantly increased desmin expression and cell permeability compared to vehicle treated podocytes. However, prior treatment with Gly attenuated the nicotine-induced desmin expression and cell permeability.Mechanistic elucidation revealed that nicotine treatment augmented the expression of toll like receptor 4 (TLR4) and pre-treatment with Gly abolished nicotine induced TLR4 upregulation.Pharmacological inhibition of TLR4 with Resatorvid, a TLR4 specific inhibitor, also attenuated nicotine induced podocyte damage. In conclusion, HMGB1 is one of the important mediators of nicotine-induced podocyte injury through TLR4 activation.

    Keywords: Podocytes, HMGB1, Nicotine, TLR4 1. Introduction, Smoking

    Received: 06 Dec 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Datta, Rahman, Koka and Boini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Krishna M Boini, University of Houston, Houston, United States

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