Related Experiment Video
Updated: Dec 6, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Sex Differences in Diabetes- and TGF-β1-Induced Renal Damage
Nadja Ziller1, Roland Kotolloshi2, Mohsen Esmaeili2
1Department of Internal Medicine III, Jena University Hospital, Am Klinikum 1, D-07747 Jena, Germany.
Abstract:
While females are less affected by non-diabetic kidney diseases compared to males, available data on sex differences in diabetic nephropathy (DN) are controversial. Although there is evidence for an imbalance of sex hormones in diabetes and hormone-dependent mechanisms in transforming growth factor β1 (TGF-β1) signaling, causes and consequences are still incompletely understood. Here we investigated the influence of sex hormones and sex-specific gene signatures in diabetes- and TGF-β1-induced renal damage using various complementary approaches (a db/db diabetes mouse model, ex vivo experiments on murine renal tissue, and experiments with a proximal tubular cell line TKPTS). Our results show that: (i) diabetes affects sex hormone concentrations and renal expression of their receptors in a sex-specific manner; (ii) sex, sex hormones and diabetic conditions influence differences in expression of TGF-β1, its receptor and bone morphogenetic protein 7 (BMP7); (iii) the sex and sex hormones, in combination with variable TGF-β1 doses, determine the net outcome in TGF-β1-induced expression of connective tissue growth factor (CTGF), a profibrotic cytokine. Altogether, these results suggest complex crosstalk between sex hormones, sex-dependent expression pattern and profibrotic signals for the precise course of DN development. Our data may help to better understand previous contradictory findings regarding sex differences in DN.
Insights
Sex hormones and diabetes influence kidney damage differently in males and females. This study reveals complex interactions affecting diabetic nephropathy (DN) progression, potentially explaining conflicting research findings.
Area of Science:
- Nephrology
- Endocrinology
- Genetics
Background:
- Diabetic nephropathy (DN) shows controversial sex differences, despite females generally being less affected by non-diabetic kidney diseases.
- Evidence suggests sex hormone imbalances in diabetes and hormone-dependent transforming growth factor β1 (TGF-β1) signaling, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the influence of sex hormones and sex-specific gene signatures on diabetes- and TGF-β1-induced renal damage.
- To elucidate the complex interplay between sex, hormones, and fibrotic signaling in diabetic kidney disease.
Main Methods:
- Utilized a db/db diabetes mouse model, ex vivo murine renal tissue, and TKPTS proximal tubular cell line.
- Examined sex-specific changes in sex hormone concentrations and renal receptor expression.
- Analyzed the impact of sex, hormones, and TGF-β1 on profibrotic cytokine (CTGF) expression.
Main Results:
- Diabetes differentially affects sex hormone levels and renal receptor expression based on sex.
- Sex, sex hormones, and diabetes modulate the expression of TGF-β1, its receptor, and BMP7.
- Sex and sex hormones, alongside TGF-β1 levels, dictate the net outcome of CTGF expression, a key profibrotic factor.
Conclusions:
- Complex crosstalk exists between sex hormones, sex-dependent gene expression, and profibrotic signals in diabetic nephropathy (DN) development.
- Findings offer insights into previously contradictory results regarding sex differences in DN.
- Understanding these sex-specific mechanisms is crucial for targeted DN therapies.
More Related Videos
Related Concept Videos
01:22Diabetes Mellitus: Overview and Type I Subtype
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
01:22Diabetes Mellitus: Type 2 and Gestational