Estrogen Protects against Renal Ischemia-Reperfusion Injury by Regulating Th17/Treg Cell Immune Balance

Zhang, Yang; Chang, Yue-Chen; Han, Zhaobin; Ma, Ketao; Zeng, Xiansi; Li, Li

doi:10.1155/2022/7812099

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…We showed that these hormones have nephroprotective effects in the case of female rats and predominantly negative effects in male rats ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Previously, it was demonstrated that a single administration of exogenous estradiol resulted in a significant reduction in pyroptosis-associated inflammation in the damaged kidney of non-ovariectomized females [ 26 ] and reduced the severity of renal injury in ovariectomized females [ 27 , 28 , 29 ]. Regarding progesterone, it has been shown that the administration of this hormone to ovariectomized female rats protected against glomerulosclerosis, decreased profibrotic factors, and eliminated other manifestations of nephropathy in a model of diabetes-associated kidney damage [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury

Andrianova,

Brezgunova,

Buyan

et al. 2024

IJMS

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The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

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Section: Discussionmentioning

confidence: 99%

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury

Andrianova,

Brezgunova,

Buyan

et al. 2024

IJMS

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“…These properties provide significant protective benefits to females, particularly in conditions that pose stress to the kidneys. Estrogen's ability to modulate various cellular pathways, such as TGF-βRI expression, modulation of Th17/Treg cell balance and Cx43 expression which further reduce renal ischemia-reperfusion injury contributes to its protective role [15][16][17] , which is more pronounced in females due to higher circulating levels of E2 compared to males. Also, during high temperature or heat stress conditions, females may receive enhanced renal protection due to the synergistic effects of E2 and heat shock protein (HSP) induction 33 .…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, sex-based physiological differences significantly influence the body's response to environmental stressors, including heat stress. Males and females exhibit distinct hormonal profiles, body compositions, and thermoregulatory mechanisms, resulting in varied susceptibility to heat stress and its subsequent impact on kidney function [15][16][17] . Recognizing these differences is essential for developing effective prevention and intervention strategies.…”

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confidence: 99%

Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study

Chen,

Wu,

et al. 2024

Sci Rep

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The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM–2 PM) and working hours (8 AM–5 PM) periods based on the participants’ residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002–1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000–1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002–1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778–0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780–0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784–0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774–0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774–0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772–0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

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“…Then the results of flow cytometry showed that Th17 cells in both blood and spleen were up-regulated in renal I/R injury mice which were then reversed by AT, and Treg cells were opposite with Th17 cells. Previous study found that Treg cell was not only present in the blood and spleen, they also infiltrate the kidney tissue after renal ischemia-reperfusion [ 33 ]. The effect of AT on Treg cells was mainly through directly increasing the number of Treg cells in the kidney tissue or promoting the transfer of cells outside the kidney to the kidney tissue, which remained to be discussed.…”

Section: Discussionmentioning

confidence: 99%