1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy
Background/Aims: A recent study has shown that 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D, can ameliorate renal dysfunction. In this study, we aimed to determine the role of 1,25-D3 in angiotensin (Ang II)-induced renal injury and investigate the underlying mechanisms involved....
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/495678 |
| _version_ | 1818965459412713472 |
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| author | Qiqi Shen Xiao Bi Lilu Ling Wei Ding |
| author_facet | Qiqi Shen Xiao Bi Lilu Ling Wei Ding |
| author_sort | Qiqi Shen |
| collection | DOAJ |
| description | Background/Aims: A recent study has shown that 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D, can ameliorate renal dysfunction. In this study, we aimed to determine the role of 1,25-D3 in angiotensin (Ang II)-induced renal injury and investigate the underlying mechanisms involved. Methods: C57BL/6J mice were treated with Ang II and/or 1,25-D3 (or saline as the control) for 2 weeks. Renal injury was evaluated using transmission electron microscopy and periodic acid-Schiff reagent and Masson’s trichrome staining. The pro-fibrotic and pro-inflammatory factors were assessed using real-time PCR. The renal apoptotic pathway was evaluated with TUNEL staining and western blot. Mitochondrial dysfunction (MtD) was determined using real-time PCR and electron microscopy. The activation of autophagy was detected using western blot. Results: In the Ang II-infused mice, expanded mesangial regions, tubulointerstitial fibrosis, and foot process fusion were observed; the levels of the pro-fibrotic and pro-inflammatory cytokines and MtD were also increased when compared with the control group. However, we found that administration of 1,25-D3 significantly improved renal function and MtD and reduced the pro-fibrotic and pro-inflammatory cytokine levels. Furthermore, 1,25-D3 significantly inhibited Ang II-induced autophagy dysfunction (determined by inhibition of Beclin-1 activation and reduction of the LC3-II/LC3-I ratio). Conclusion: Our findings suggest that 1,25-D3 may attenuate Ang II-induced renal injury by improving MtD and modulating autophagy. 1,25-D3 may be a new therapeutic for the treatment of CKD. |
| first_indexed | 2024-12-20T13:17:21Z |
| format | Article |
| id | doaj.art-c4c16d88dbdf4fbfabc1f4a3bcbd3668 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T13:17:21Z |
| publishDate | 2018-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c4c16d88dbdf4fbfabc1f4a3bcbd36682022-12-21T19:39:30ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-11-015141751176210.1159/0004956784956781,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and AutophagyQiqi ShenXiao BiLilu LingWei DingBackground/Aims: A recent study has shown that 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D, can ameliorate renal dysfunction. In this study, we aimed to determine the role of 1,25-D3 in angiotensin (Ang II)-induced renal injury and investigate the underlying mechanisms involved. Methods: C57BL/6J mice were treated with Ang II and/or 1,25-D3 (or saline as the control) for 2 weeks. Renal injury was evaluated using transmission electron microscopy and periodic acid-Schiff reagent and Masson’s trichrome staining. The pro-fibrotic and pro-inflammatory factors were assessed using real-time PCR. The renal apoptotic pathway was evaluated with TUNEL staining and western blot. Mitochondrial dysfunction (MtD) was determined using real-time PCR and electron microscopy. The activation of autophagy was detected using western blot. Results: In the Ang II-infused mice, expanded mesangial regions, tubulointerstitial fibrosis, and foot process fusion were observed; the levels of the pro-fibrotic and pro-inflammatory cytokines and MtD were also increased when compared with the control group. However, we found that administration of 1,25-D3 significantly improved renal function and MtD and reduced the pro-fibrotic and pro-inflammatory cytokine levels. Furthermore, 1,25-D3 significantly inhibited Ang II-induced autophagy dysfunction (determined by inhibition of Beclin-1 activation and reduction of the LC3-II/LC3-I ratio). Conclusion: Our findings suggest that 1,25-D3 may attenuate Ang II-induced renal injury by improving MtD and modulating autophagy. 1,25-D3 may be a new therapeutic for the treatment of CKD.https://www.karger.com/Article/FullText/4956781,25-Dihydroxyvitamin D3Mitochondrial dysfunction AutophagyAngiotensin II |
| spellingShingle | Qiqi Shen Xiao Bi Lilu Ling Wei Ding 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy Cellular Physiology and Biochemistry 1,25-Dihydroxyvitamin D3 Mitochondrial dysfunction Autophagy Angiotensin II |
| title | 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy |
| title_full | 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy |
| title_fullStr | 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy |
| title_full_unstemmed | 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy |
| title_short | 1,25-Dihydroxyvitamin D3 Attenuates Angiotensin II-Induced Renal Injury by Inhibiting Mitochondrial Dysfunction and Autophagy |
| title_sort | 1 25 dihydroxyvitamin d3 attenuates angiotensin ii induced renal injury by inhibiting mitochondrial dysfunction and autophagy |
| topic | 1,25-Dihydroxyvitamin D3 Mitochondrial dysfunction Autophagy Angiotensin II |
| url | https://www.karger.com/Article/FullText/495678 |
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