Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule
Shiga toxin-producing <i>Escherichia coli</i> (STEC) causes proximal tubular defects in the kidney. However, factors altered by Shiga toxin (Stx) within the proximal tubules are yet to be shown. We determined Stx receptor Gb3 in murine and human kidneys and confirmed the receptor express...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/14/2/69 |
| _version_ | 1797476263691026432 |
|---|---|
| author | Fumiko Obata Ryo Ozuru Takahiro Tsuji Takashi Matsuba Jun Fujii |
| author_facet | Fumiko Obata Ryo Ozuru Takahiro Tsuji Takashi Matsuba Jun Fujii |
| author_sort | Fumiko Obata |
| collection | DOAJ |
| description | Shiga toxin-producing <i>Escherichia coli</i> (STEC) causes proximal tubular defects in the kidney. However, factors altered by Shiga toxin (Stx) within the proximal tubules are yet to be shown. We determined Stx receptor Gb3 in murine and human kidneys and confirmed the receptor expression in the proximal tubules. Stx2-injected mouse kidney tissues and Stx2-treated human primary renal proximal tubular epithelial cell (RPTEC) were collected and microarray analysis was performed. We compared murine kidney and RPTEC arrays and selected common 58 genes that are differentially expressed vs. control (0 h, no toxin-treated). We found that the most highly expressed gene was GDF15, which may be involved in Stx2-induced weight loss. Genes associated with previously reported Stx2 activities such as src kinase Yes phosphorylation pathway activation, unfolded protein response (UPR) and ribotoxic stress response (RSR) showed differential expressions. Moreover, circadian clock genes were differentially expressed, suggesting Stx2-induced renal circadian rhythm disturbance. Circadian rhythm-regulated proximal tubular Na<sup>+</sup>-glucose transporter SGLT1 (SLC5A1) was down-regulated, indicating proximal tubular functional deterioration, and mice developed glucosuria confirming proximal tubular dysfunction. Stx2 alters gene expression in murine and human proximal tubules through known activities and newly investigated circadian rhythm disturbance, which may result in proximal tubular dysfunctions. |
| first_indexed | 2024-03-09T20:56:28Z |
| format | Article |
| id | doaj.art-72c24c29fe354d759c90f8d5519e1ab6 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T20:56:28Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-72c24c29fe354d759c90f8d5519e1ab62023-11-23T22:20:53ZengMDPI AGToxins2072-66512022-01-011426910.3390/toxins14020069Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal TubuleFumiko Obata0Ryo Ozuru1Takahiro Tsuji2Takashi Matsuba3Jun Fujii4Division of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago 683-8503, JapanDepartment of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, JapanDivision of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago 683-8503, JapanDivision of Infectious Disease Control and Prevention, Department of Animal Pharmaceutical Science, School of Pharmaceutical Science, Kyusyu University of Health and Welfare, 1714-1 Yoshino-machi, Nobeoka 882-8508, JapanDivision of Bacteriology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago 683-8503, JapanShiga toxin-producing <i>Escherichia coli</i> (STEC) causes proximal tubular defects in the kidney. However, factors altered by Shiga toxin (Stx) within the proximal tubules are yet to be shown. We determined Stx receptor Gb3 in murine and human kidneys and confirmed the receptor expression in the proximal tubules. Stx2-injected mouse kidney tissues and Stx2-treated human primary renal proximal tubular epithelial cell (RPTEC) were collected and microarray analysis was performed. We compared murine kidney and RPTEC arrays and selected common 58 genes that are differentially expressed vs. control (0 h, no toxin-treated). We found that the most highly expressed gene was GDF15, which may be involved in Stx2-induced weight loss. Genes associated with previously reported Stx2 activities such as src kinase Yes phosphorylation pathway activation, unfolded protein response (UPR) and ribotoxic stress response (RSR) showed differential expressions. Moreover, circadian clock genes were differentially expressed, suggesting Stx2-induced renal circadian rhythm disturbance. Circadian rhythm-regulated proximal tubular Na<sup>+</sup>-glucose transporter SGLT1 (SLC5A1) was down-regulated, indicating proximal tubular functional deterioration, and mice developed glucosuria confirming proximal tubular dysfunction. Stx2 alters gene expression in murine and human proximal tubules through known activities and newly investigated circadian rhythm disturbance, which may result in proximal tubular dysfunctions.https://www.mdpi.com/2072-6651/14/2/69Shiga toxin type 2 (Stx2)renal proximal tubulemousehuman renal proximal tubular epithelial cell (RPTEC)microarraycircadian rhythm |
| spellingShingle | Fumiko Obata Ryo Ozuru Takahiro Tsuji Takashi Matsuba Jun Fujii Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule Toxins Shiga toxin type 2 (Stx2) renal proximal tubule mouse human renal proximal tubular epithelial cell (RPTEC) microarray circadian rhythm |
| title | Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule |
| title_full | Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule |
| title_fullStr | Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule |
| title_full_unstemmed | Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule |
| title_short | Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule |
| title_sort | stx2 induces differential gene expression and disturbs circadian rhythm genes in the proximal tubule |
| topic | Shiga toxin type 2 (Stx2) renal proximal tubule mouse human renal proximal tubular epithelial cell (RPTEC) microarray circadian rhythm |
| url | https://www.mdpi.com/2072-6651/14/2/69 |
| work_keys_str_mv | AT fumikoobata stx2inducesdifferentialgeneexpressionanddisturbscircadianrhythmgenesintheproximaltubule AT ryoozuru stx2inducesdifferentialgeneexpressionanddisturbscircadianrhythmgenesintheproximaltubule AT takahirotsuji stx2inducesdifferentialgeneexpressionanddisturbscircadianrhythmgenesintheproximaltubule AT takashimatsuba stx2inducesdifferentialgeneexpressionanddisturbscircadianrhythmgenesintheproximaltubule AT junfujii stx2inducesdifferentialgeneexpressionanddisturbscircadianrhythmgenesintheproximaltubule |