Sex Differences in Diabetes- and TGF-β1-Induced Renal Damage

Ziller, Nadja; Kotolloshi, Roland; Esmaeili, Mohsen; Liebisch, Marita; Mrowka, Ralf; Baniahmad, Aria; Liehr, Thomas; Wolf, Günter; Loeffler, Ivonne

doi:10.3390/cells9102236

Cited by 30 publications

(32 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…54 The sex differences do not significantly affect lifespan in laboratory mice 54 and our findings that female eI-F2A-KO mice have lower longevity in comparison with the eIF2A-KO male mice suggests that eIF2A may affect sexspecific signaling pathways. Accumulating data do reveal sex specific difference in several signaling pathways (such as e.g., TGF-βsignaling 55 ) and suggest, for example, that diabetes may be associated with an imbalance in sex hormone levels, but it has not yet been conclusively clarified how the levels of testosterone and/or estrogen and their respective receptors and the imbalance between them are exactly related to the differences in disease progression in both sexes. 56,57 We also examined if locomotor activity and daily/circadian rhythms of locomotor activity were affected in eI-F2A-KO mice.…”

Section: Discussionmentioning

confidence: 99%

eIF2A‐knockout mice reveal decreased life span and metabolic syndrome

et al. 2021

View full text Add to dashboard Cite

Eukaryotic initiation factor 2A (eIF2A) is a 65 kDa protein that functions in minor initiation pathways, which affect the translation of only a subset of messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)containing mRNAs and/or mRNAs harboring upstream near cognate/non-AUG start codons. These non-canonical initiation events are important for regulation of protein synthesis during cellular development and/or the integrated stress response. Selective eIF2A knockdown in cellular systems significantly inhibits

show abstract

Section: Discussionmentioning

confidence: 99%

eIF2A‐knockout mice reveal decreased life span and metabolic syndrome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In nondiabetic conditions, men with chronic kidney disease of various etiologies show a more rapid decline in renal function than women 21 ; however, a study suggested diabetic nephropathy progression to be faster in women, 21 and the difference might be related to female hormones. A recent study published in the journal Cells investigated the extent to which sex hormones play a role in sex differences in both diabetes and transforming growth factor β1 (TGF‐β1)‐induced renal damage 22 . They found that both genetic repertoire and sex hormones can determine sex differences in diabetic nephropathy, and hormones and sex in combination with TGF‐β1 dose determine whether TGF‐β1 exerts pro‐ or antifibrotic effects.…”

Section: Discussionmentioning

confidence: 99%

A study on the status of normoalbuminuric renal insufficiency among type 2 diabetes mellitus patients: A multicenter study based on a Chinese population

Jia

Zang

Pang

et al. 2021

Journal of Diabetes

View full text Add to dashboard Cite

Background: Patients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population.Methods: We included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin-to-creatinine ratio (UACR), participants were stratified into four groups-normal albuminuria, albuminuria, normoalbuminuria with eGFR < 60 mL/min/1.73 m 2 , and albuminuria with eGFR < 60 mL/min/1.73 m 2 . Clinical parameters and characteristics of patients with normoalbuminuria and eGFR < 60 mL/min/1.73 m 2 were retrospectively analyzed.Results: A total of 1060 out of 8131 individuals with diabetes had decreased eGFR (<60 mL/min/1.73 m 2 ). Normoalbuminuria accounted for 63.3% of participants with eGFR < 60 mL/min/1.73 m 2 , and microalbuminuria and macroalbuminuria accounted for 30.1% and 6.3%, respectively. Patients with normoalbuminuria and reduced eGFR were more frequently male, older, and had higher levels of triglycerides than patients with normal albuminuria and eGFR. We also detected a correlation between lower extremity arterial disease, newly diagnosed diabetes, and normoalbuminuria-reduced eGFR. Compared with participants with both albuminuria and eGFR decline, those with normoalbuminuria had better metabolic indicators, including systolic blood pressure and glycosylated hemoglobin, and shorter diabetes duration. Even in the normal range, UACR has a significant correlation with the risk of eGFR insufficiency.Conclusions: Normoalbuminuric renal insufficiency, characterized by male sex, older age, a higher level of triglyceride levels, and a higher risk of lower Xiaomeng Jia and Li Zang contributed equally to this work.

show abstract

“…TGF-β1 is a major cytokine secreted by mesangial cells that mediates the development of DN [33] . TGF-β1 is a key cytokine mediating collagen deposition in kidney, including promoting the production of ECM, inhibiting the degradation of ECM and participating in renal brosis [34,35] . ECM of DN patients is produced by mesangial cells and mainly consists of bronectin, type IV collagen and a small amount of type I collagen.…”

Section: Discussionmentioning

confidence: 99%

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

Huang

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Oxidative stress and its induced inflammation are important pathological processes of diabetic nephropathy (DN). Oridonin, a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory properties, it is also a newly reported NLRP3 inhibitor. However, the renoprotective effects of Oridonin and the underlying molecular mechanisms have not been explored in DN. We hypothesized that Oridonin could reduce NLRP3 pathway and ameliorate diabetes‑induced renal fibrosis.Methods: We used STZ-induced diabetic rats combined high-fat diet to establish a T2DM animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. In addition, the expression of inflammatory factors and fibrotic markers were analyzed by western blot.Results: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the 10 mg/kg/day group and 20 mg/kg/day group compared to the T2DM group. Moreover, the expression levels of TXNIP/NLRP3 and NF‑κB pathway were decreased in the Oridonin treatment group compared to non-treated group. Conclusions: The NLRP3-inflammasome inhibitor Oridonin reduces renal fibrosis and preserves kidney function in T2DM rat model, which indicates potential therapeutic effect of Oridonin on DN.

show abstract

Sex Differences in Diabetes- and TGF-β1-Induced Renal Damage

Cited by 30 publications

References 81 publications

eIF2A‐knockout mice reveal decreased life span and metabolic syndrome

eIF2A‐knockout mice reveal decreased life span and metabolic syndrome

A study on the status of normoalbuminuric renal insufficiency among type 2 diabetes mellitus patients: A multicenter study based on a Chinese population

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

Contact Info

Product

Resources

About