| First Author | Jiang N | Year | 2020 |
| Journal | Cell Prolif | Volume | 53 |
| Issue | 11 | Pages | e12909 |
| PubMed ID | 32975326 | Mgi Jnum | J:297923 |
| Mgi Id | MGI:6479412 | Doi | 10.1111/cpr.12909 |
| Citation | Jiang N, et al. (2020) HIF-1alpha ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics. Cell Prolif 53(11):e12909 |
| abstractText | OBJECTIVES: In diabetic nephropathy (DN), hypoxia-inducible factor-1alpha (HIF-1alpha) activation in tubular cells plays an important protective role against kidney injury. The effects may occur via the target genes of HIF-1alpha, such as haem oxygenase-1 (HO-1), but the exact mechanisms are incompletely understood. MATERIALS AND METHODS: Mice with proximal tubule-specific knockout of HIF-1alpha (PT-HIF-1alpha(-/-) mice) were generated, and diabetes was induced in these mice by streptozotocin (STZ) injection. In addition, to mimic a hypoxic state, cobaltous chloride (CoCl2 ) was applied to HK-2 cells. RESULTS: Our study first verified that conditional knockout of HIF-1alpha worsened tubular injury in DN; additionally, aggravated kidney dysfunction, renal histopathological alterations, mitochondrial fragmentation, ROS accumulation and apoptosis were observed in diabetic PT-HIF-1alpha(-/-) mice. In vitro study showed that compared to control group, HK-2 cells cultured under hypoxic ambiance displayed increased mitochondrial fragmentation, ROS production, mitochondrial membrane potential loss and apoptosis. These increases were reversed by overexpression of HIF-1alpha or treatment with a HO-1 agonist. Importantly, cotreatment with a HIF-1alpha inhibitor and a HO-1 agonist rescued the HK-2 cells from the negative impacts of the HIF-1alpha inhibitor. CONCLUSIONS: These data revealed that HIF-1alpha exerted a protective effect against tubular injury in DN, which could be mediated via modulation of mitochondrial dynamics through HO-1 upregulation. |
