High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury
IntroductionCigarette 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 as...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1540639/full |
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| author | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini |
| author_facet | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini |
| author_sort | Sayantap Datta |
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| description | IntroductionCigarette 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.Methods and ResultsBiochemical 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.ConclusionHMGB1 is one of the important mediators of nicotine‐induced podocyte injury through TLR4 activation. |
| format | Article |
| id | doaj-art-b4ce68a639784d77af1f94e397c641b4 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-b4ce68a639784d77af1f94e397c641b42025-01-07T06:43:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15406391540639High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injurySayantap Datta0Mohammad Atiqur Rahman1Saisudha Koka2Krishna M. Boini3Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United StatesDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United StatesDepartment of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX, United StatesDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United StatesIntroductionCigarette 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.Methods and ResultsBiochemical 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.ConclusionHMGB1 is one of the important mediators of nicotine‐induced podocyte injury through TLR4 activation.https://www.frontiersin.org/articles/10.3389/fphar.2024.1540639/fullpodocytesHMGB1nicotineTLR4smoking |
| spellingShingle | Sayantap Datta Mohammad Atiqur Rahman Saisudha Koka Krishna M. Boini High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury Frontiers in Pharmacology podocytes HMGB1 nicotine TLR4 smoking |
| title | High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury |
| title_full | High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury |
| title_fullStr | High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury |
| title_full_unstemmed | High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury |
| title_short | High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury |
| title_sort | high mobility group box 1 hmgb1 mediates nicotine induced podocyte injury |
| topic | podocytes HMGB1 nicotine TLR4 smoking |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1540639/full |
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