Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells

Ding, Xian Fei; Sun, Min; Guan, Fang Xia; Guo, Li; Zhang, Yan Yan; Wan, You Dong; Zhang, Xiao Juan; Yu, Yan Wu; Shan, Shan; Yao, Hai; Yao, Rui; Zhang, Rui Fang; Kan, Quan Cheng

doi:10.1093/ajh/hpx117

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…IHC staining of CRC tissue samples and xenografted tumors was performed as described previously [40]. Sections were incubated with primary antibody PHLDA2 (Bs-6884R; 1:100), KI67 (ab15580; 1:200).…”

Section: Immunohistochemistry (Ihc) and Immunofluorescence (If)mentioning

confidence: 99%

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Lou

Jiang

2020

Aging

105

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High levels of the imprinted gene pleckstrin homology like domain family A member 2 (PHLDA2) correlate with tumor progression in several malignancies. Here, we investigated the effects of PHDLDA2 expression in CRC through assays of cellular proliferation, invasion, migration, and apoptosis. We also screened for possible mechanisms of action. Our results show that PHLDA2 was upregulated in CRC tissues. Knockdown of PHLDA2 inhibited cellular proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in vitro. Knockout of PHLDA2 promoted cellular apoptosis, in part by activating autophagy. PHLDA2 knockout also inhibited tumorigenesis and expression of KI67 protein in vivo. The effects of PHLDA2 on autophagy and EMT were mediated in part via the PI3K/AKT signaling pathway. Taken together, these results suggest that downregulation of PHLDA2 inhibits tumor growth and PI3K, thereby promoting autophagy and inhibiting EMT, in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3β signaling pathways.

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Section: Immunohistochemistry (Ihc) and Immunofluorescence (If)mentioning

confidence: 99%

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Lou

Jiang

2020

Aging

105

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“…H&E staining was used to evaluate the lung tissue from the rats. The procedure has been described in detail in the related literature [64]. The lung tissue was resected at a size of 5 μm and sectioned.…”

Section: Histological Analysis Of Rat Lungsmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

et al. 2020

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Background We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes. Methods A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing. Results The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota. Conclusions Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.

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“…Compared with the aforementioned studies on prematurity and IUGR and their effect on glomerular vasculogenesis, research involving chorioamnionitis has focused on the postnatal effect on RAS and the subsequent development of hypertension—one of the known long-term consequences of perinatal stress. Ding et al and Hao et al showed in rodent models that chorioamnionitis increased the intrarenal expression of renin and angiotensin II in the weeks after birth without elevated levels of plasma renin activity or angiotensin II [ 68 , 69 ]. Hypertension developed simultaneously with the rise in intrarenal RAS.…”

Section: Vascular Developmentmentioning

confidence: 99%

“…Another effect of chorioamnionitis on the glomerular capillaries is the correlation between chorioamnionitis and glomerulovascular damage rendering the glomeruli increasingly susceptible for glomerulosclerosis [ 71 ]. Kidneys exposed to LPS during development show more apoptosis at birth, mainly originating from glomerular endothelial cells [ 69 ]. Guo et al showed that in adulthood, the glomeruli show increase in mesangial matrix, deposition of collagen 1 and 3 and upregulation of α-SMA in the interstitium [ 71 ].…”

Section: Vascular Developmentmentioning

confidence: 99%

Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy

et al. 2020

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Prematurity and perinatal stress, such as intrauterine growth restriction (IUGR) and chorioamnionitis, are pathological processes creating an impaired intrauterine environment. These intrauterine factors are associated with the development of proteinuria, hypertension, and chronic kidney disease (CKD) later in life. Initially, this was thought to be secondary to oligonephropathy, subsequent glomerular hypertrophy, and hyperfiltration, leading to glomerulosclerosis, a further decrease in nephron number, and finally CKD. Nowadays, there is increasing evidence that prematurity and perinatal stress affect not only nephron endowment but also the maturation of podocytes and vasculogenesis. IUGR is associated with podocyte damage and an aggravated course of nephrotic syndrome. Moreover, preterm birth and IUGR are known to cause upregulation of the postnatal reninangiotensin system, resulting in hypertension. Chorioamnionitis causes damage to the glomeruli, thereby predisposing to the development of glomerulosclerosis. This review aims to summarize current knowledge on the influence of prematurity, IUGR, and chorioamnionitis on the development of different glomerular structures. After summarizing human and experimental data on low nephron number in general, a specific focus on the current understanding of podocyte and glomerular capillary formation in relation to prematurity and different causes of perinatal stress is presented.

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Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells

Cited by 6 publications

References 24 publications

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy

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