Galectin-3 and Autophagy in Renal Acute Tubular Necrosis
Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3604 |
| _version_ | 1797212605666820096 |
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| author | Suhail Al-Salam Govindan S. Jagadeesh Manjusha Sudhadevi Javed Yasin |
| author_facet | Suhail Al-Salam Govindan S. Jagadeesh Manjusha Sudhadevi Javed Yasin |
| author_sort | Suhail Al-Salam |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 <<sup>tm 1 Poi</sup>>/J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins’ expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (<i>p</i> < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN. |
| first_indexed | 2024-04-24T10:45:03Z |
| format | Article |
| id | doaj.art-ee9229e293b2433c8c97c29fdb9e5038 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:45:03Z |
| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ee9229e293b2433c8c97c29fdb9e50382024-04-12T13:19:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257360410.3390/ijms25073604Galectin-3 and Autophagy in Renal Acute Tubular NecrosisSuhail Al-Salam0Govindan S. Jagadeesh1Manjusha Sudhadevi2Javed Yasin3Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Alain P.O. Box 15551, United Arab EmiratesDepartment of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Alain P.O. Box 15551, United Arab EmiratesDepartment of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Alain P.O. Box 15551, United Arab EmiratesDepartment of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Alain P.O. Box 15551, United Arab EmiratesAcute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 <<sup>tm 1 Poi</sup>>/J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins’ expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (<i>p</i> < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN.https://www.mdpi.com/1422-0067/25/7/3604kidneyacute tubular necrosisgalectin-3autophagymacroautophagycell survival signals |
| spellingShingle | Suhail Al-Salam Govindan S. Jagadeesh Manjusha Sudhadevi Javed Yasin Galectin-3 and Autophagy in Renal Acute Tubular Necrosis International Journal of Molecular Sciences kidney acute tubular necrosis galectin-3 autophagy macroautophagy cell survival signals |
| title | Galectin-3 and Autophagy in Renal Acute Tubular Necrosis |
| title_full | Galectin-3 and Autophagy in Renal Acute Tubular Necrosis |
| title_fullStr | Galectin-3 and Autophagy in Renal Acute Tubular Necrosis |
| title_full_unstemmed | Galectin-3 and Autophagy in Renal Acute Tubular Necrosis |
| title_short | Galectin-3 and Autophagy in Renal Acute Tubular Necrosis |
| title_sort | galectin 3 and autophagy in renal acute tubular necrosis |
| topic | kidney acute tubular necrosis galectin-3 autophagy macroautophagy cell survival signals |
| url | https://www.mdpi.com/1422-0067/25/7/3604 |
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