Table 4 Additional regulation of ACE2 mRNA levels
From: ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification
Additional regulation of ACE2 mRNA levels | ||
|---|---|---|
Name | Description | Ref. |
Upregulation | ||
 Apelin | Active apelin enhances ACE2 transcription in apelin receptor-overexpressing cardiomyocytes Loss of apelin or apelin receptor leads to a reduction of heart contractility in mice | [85] |
 ELA | Ang II-induced ACE2 mRNA levels are restored by treatment of ELA The ELA expression is low in vascular injury-associated hypertension | [88] |
 IL-1β | IL-1β treatment increases ACE2 mRNA levels in human osteosarcoma cells | [92] |
 CH3IL1 | CH3IL1 recombinant protein stimulates ACE2 mRNA levels in human lung epithelial cells CH3IL1 is highly expressed in the lung tissues of patients with aging, cardiovascular disease, and chronic lung disease Circulating CH3IL1 levels are increased in aging, hypertension, and severe COVID-19 CH3IL1-induced ACE2 mRNA levels are blocked by the CH3IL1 inhibitor kasugamycin | [10] |
Downregulation | ||
 Nrf2 | Nrf2 knockout restores ACE2 mRNA and protein levels in renal proximal tubular cells of type 1 diabetes mice Nrf2 levels are increased in the renal proximal tubules of 20-week-old type 1 diabetes mice High-glucose-reduced ACE2 mRNA levels are restored by the Nrf2 inhibitor trigonelline | [24] |
 miR-143 | miR-143 levels are increased in the aortas of spontaneously hypertensive rats, whereas ACE2 mRNA and protein levels are decreased | |
 AT1R | Ang II-AT1R axis downregulates ACE2 through AT1R in human kidney epithelial cells Ang II-mediated ACE2 mRNA reduction is rescued by the AT1R inhibitor losartan | [103] |
 IL-13 | IL-13 signaling reduces ACE2 gene expression in human airway epithelial cells | |
 TGF-β | TGF-β signaling inhibits ACE2 gene expression in renal tubular cells TGF-β overproduction in the renal tissues contributes to the pathogenesis of diabetic nephropathy High-glucose-inhibited ACE2 mRNA levels are restored by the TGF-β receptor inhibitor SB431542 | [108] |
 Estrogen | Estrogen treatment decreases ACE2 mRNA levels in normal human bronchial epithelial cells The estrogen 17β-estradiol decreases renal ACE2 enzyme activity in the sex-chromosome-independent manner | |
 Miz1 | ACE2 mRNA levels are increased in the MIZ1-deficient mice | [113] |
 HIF-1α | ACE2 mRNA levels are inhibited by HIF-1α | [114] |
 TNF-α | ACE2 mRNA levels may be decreased by TNF-α signaling in the ileum of Crohn’s disease parents | [117] |