ArticleLaboratory investigation; a journal of technical methods and pathology2018
Sex dimorphism in ANGII-mediated crosstalk between ACE2 and ACE in diabetic nephropathy.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Sex Differences in the Cardiovascular Significance of Albuminuria in Type 2 Diabetes: A Narrative Review.Journal of clinical medicine · 2026Review
- Global Adam17 Deficiency Preserves Renal Function and Modulates Integrated Pathogenic Responses in Experimental Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- Canagliflozin Promotes Structural and Functional Changes in Proximal Tubular Cell Mitochondria of Hypertensive-Diabetic Mice.International journal of molecular sciences · 2025Article
- Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.Clinical and experimental nephrology · 2025Article
- Gender-related diabetic nephropathy: Yes or no.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024Article
- SGLT2i and GLP1-RA exert additive cardiorenal protection with a RAS blocker in uninephrectomized db/db mice.Frontiers in pharmacology · 2024Article
- Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats.International journal of molecular sciences · 2023Article
- Role of sex hormones in diabetic nephropathy.Frontiers in endocrinology · 2023Review
- Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.International journal of molecular sciences · 2022Article
- Angiotensin II and ATInternational journal of molecular sciences · 2022Review
- Children With Short Stature Display ReducedFrontiers in endocrinology · 2022Article
- Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?The Journal of infectious diseases · 2021Article
- Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes.International journal of molecular sciences · 2021Article
- Article
- Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.Clinical science (London, England : 1979) · 2021Article
- The beneficial effects of menopausal hormone therapy on renal survival in postmenopausal Korean women from a nationwide health survey.Scientific reports · 2021Article
- Human cell receptors: potential drug targets to combat COVID-19.Amino acids · 2021Review
- Novel roles of the renal angiotensin-converting enzyme.Molecular and cellular endocrinology · 2021Review
- Determinants of prolonged viral RNA shedding in hospitalized patients with SARS-CoV-2 infection.Diagnostic microbiology and infectious disease · 2021Article
- Both Specific Endothelial and Proximal Tubular Adam17 Deletion Protect against Diabetic Nephropathy.International journal of molecular sciences · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2. In the present work, we aimed to study the sex-specific susceptibility to diabetes and direct infusion of ANGII in kidney disease progression, with a special focus on its link to ACE2 and ACE. In our mouse model, ANGII promoted hypertension, albuminuria, reduced glomerular filtration, and glomerular histological alterations. ANGII adverse effects were accentuated by diabetes and ACE2 deficiency, in a sex-dependent fashion: ACE2 deficiency accentuated ANGII-induced hypertension, albuminuria, and glomerular hypertrophy in diabetic females, whereas in diabetic males exacerbated ANGII-mediated glomerular hypertrophy, mesangial expansion, and podocyte loss. At the molecular level, ANGII downregulated renal ACE gene and enzymatic activity levels, as well as renin gene expression in ACE2KO mice. Interestingly, male sex and diabetes accentuated this effect. Here we show sex dimorphism in the severity of diabetes- and ANGII-related renal lesions, and demonstrate that ACE2- and ACE-related compensatory mechanisms are sex-specific. Supporting our previous findings, the modulation and ANGII-mediated crosstalk between ACE2 and ACE in DN progression was more evident in males. This work increases the understanding of the sex-specific role of ACE2 and ACE in DN, reinforcing the necessity of more personalized treatments targeting RAS.
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