Dataset Information

HIF-1α ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics.

ABSTRACT:

Objectives

In diabetic nephropathy (DN), hypoxia-inducible factor-1α (HIF-1α) activation in tubular cells plays an important protective role against kidney injury. The effects may occur via the target genes of HIF-1α, 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-1α (PT-HIF-1α^-/- 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-1α worsened tubular injury in DN; additionally, aggravated kidney dysfunction, renal histopathological alterations, mitochondrial fragmentation, ROS accumulation and apoptosis were observed in diabetic PT-HIF-1α^-/- 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-1α or treatment with a HO-1 agonist. Importantly, cotreatment with a HIF-1α inhibitor and a HO-1 agonist rescued the HK-2 cells from the negative impacts of the HIF-1α inhibitor.

Conclusions

These data revealed that HIF-1α exerted a protective effect against tubular injury in DN, which could be mediated via modulation of mitochondrial dynamics through HO-1 upregulation.

SUBMITTER: Jiang N

PROVIDER: S-EPMC7653251 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

HIF-1α ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics.

Jiang Na N Zhao Hao H Han Yachun Y Li Li L Xiong Shan S Zeng Lingfeng L Xiao Ying Y Wei Ling L Xiong Xiaofen X Gao Peng P Yang Ming M Liu Yu Y Sun Lin L

Cell proliferation 20200925 11

<h4>Objectives</h4>In diabetic nephropathy (DN), hypoxia-inducible factor-1α (HIF-1α) activation in tubular cells plays an important protective role against kidney injury. The effects may occur via the target genes of HIF-1α, such as haem oxygenase-1 (HO-1), but the exact mechanisms are incompletely understood.<h4>Materials and methods</h4>Mice with proximal tubule-specific knockout of HIF-1α (PT-HIF-1α<sup>-/-</sup> mice) were generated, and diabetes was induced in these mice by streptozotocin ...[more]

PMID: 32975326

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Dataset Information

HIF-1α ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics.

Objectives

Materials and methods

Results

Conclusions

Publications

HIF-1α ameliorates tubular injury in diabetic nephropathy via HO-1-mediated control of mitochondrial dynamics.

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