| First Author | Han M | Year | 2021 |
| Journal | Am J Physiol Renal Physiol | Volume | 320 |
| Issue | 3 | Pages | F308-F321 |
| PubMed ID | 33427060 | Mgi Jnum | J:323058 |
| Mgi Id | MGI:6714599 | Doi | 10.1152/ajprenal.00577.2020 |
| Citation | Han M, et al. (2021) Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 320(3):F308-F321 |
| abstractText | Renal ischemia-reperfusion (I/R) injury is associated with markedly reduced protein expression of aquaporins (AQPs). Membrane G protein-coupled bile acid receptor-1 (TGR5) has shown protective roles in some kidney diseases. The purpose of the current study was to investigate whether activation of TGR5 prevented the decreased protein expression of AQPs in rodents with renal I/R injury and potential mechanisms. TGR5 agonist lithocholic acid (LCA) treatment reduced polyuria after renal I/R injury in rats. LCA prevented the decreased abundance of AQP2 protein and upregulated hypoxia-inducible factor (HIF)-1alpha protein expression, which were associated with decreased protein abundance of NF-kappaB p65 and IL-1beta. After renal I/R, mice with tgr5 gene deficiency exhibited further decreases in AQP2 and HIF-1alpha protein abundance and increases of IL-1beta and NF-kappaB p65 protein expression compared with wild-type mice. In primary cultured inner medullary collecting duct cells with hypoxia/reoxygenation, LCA induced markedly increased protein expression of AQP2 and HIF-1alpha, which were partially prevented by the PKA inhibitor H89. FG4592, a prolyl-4-hydroxylase domain-containing protein inhibitor, increased HIF-1alpha and AQP2 protein abundance in association with decreased NF-kappaB p65 protein expression in inner medullary collecting duct cells with hypoxia/reoxygenation. In conclusion, TGR5 stimulation by LCA prevented downregulation of renal AQPs in kidney with I/R injury, likely through activating HIF-1alpha signaling and suppressing inflammatory responses.NEW & NOTEWORTHY Stimulation of the membrane G protein-coupled bile acid receptor TGR5 by lithocholic acid (LCA) reduced polyuria in rats with renal ischemia-reperfusion (I/R) injury. LCA increased abundance of aquaporin-2 (AQP2) protein and upregulated hypoxia-inducible factor (HIF)-1alpha protein expression in association with decreased NF-kappaB p65 and IL-1beta. After I/R, mice with tgr5 gene deficiency exhibited more severe decreases in AQP2 and HIF-1alpha protein abundance and inflammatory responses. TGR5 activation exhibits a protective role in acute renal injury induced by I/R. |
