Effects of acute intra-abdominal hypertension on multiple intestinal barrier functions in rats

Leng, Yuxin; Yi, Min; Fan, Jie; Bai, Yu; Ge, Qi; Yao, Gaiqi

doi:10.1038/srep22814

Cited by 43 publications

(38 citation statements)

References 53 publications

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“…24 We found that as the IAP increases to 20 mm Hg for 90 min, intestinal barriers become seriously disrupted and dysbiosis occurs. 25 However, in the present study, at the same level of IAH, MICU1 exhibited a compensatory response towards the increased intestinal permeability, indicating that under IAH, the gut promotes a self-protective mechanism. Further studies would be needed to establish whether MICU1 would be disrupted as the course/degree of IAH progresses, and to determine what roles are played by MICU1 in the subsequent abdominal compartment syndrome and gut-derived sepsis.…”

Section: Discussioncontrasting

confidence: 62%

MICU1 may be a promising intervention target for gut-derived sepsis induced by intra-abdominal hypertension

Leng

Zhao

et al. 2016

Cell Death Discovery

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Intra-abdominal hypertension (IAH) is a common and serious complication in critically ill patients, for which there is no targeted therapy. IAH-induced dysfunction of intestinal barriers is closely associated with oxidative imbalances, which are considered to provide a pathophysiological basis for subsequent gut-derived sepsis. However, the upstream mechanism that produces oxidative damage during IAH remains unknown. It is not clear whether ‘mitochondrial Ca2+ uptake 1’ (MICU1, the key protein regulating the oxidative process) is involved in preventing Ca2+m (mitochondrial Ca2+) overload. Here, we detected changes in the expression of MICU1 during the development of increased intestinal permeability in rats with IAH, and we explored the related mechanism regulating epithelial-barrier functions by knocking-down micu1 in Caco-2 cells. Our results demonstrated that, to combat IAH-induced dysfunction of intestinal barriers, MICU1 undergoes a compensatory increase in expression, whereas ‘mitochondrial calcium uniporter’ (MCU) – a conserved Ca2+ transporter – becomes transcriptionally suppressed. Silencing the expression of MICU1 destroyed Caco-2 cell barrier integrity, promoted paracellular permeability, and impaired the expression of tight junction proteins (occludin, ZO-1, and claudin 1). Meanwhile, oxidative imbalances were induced; malondialdehyde (MDA), a product of oxidation, was increased and antioxidant products (GSH-Px, CAT, and SOD) were decreased. In MICU1-deficient Caco-2 cells, proliferation was inhibited and apoptosis was promoted. Collectively, our results indicate that MICU1-related oxidation/antioxidation disequilibrium is strongly involved in IAH-induced damage to intestinal barriers. MICU1-targeted treatment may hold promise for preventing the progression of IAH to gut-derived sepsis.

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Section: Discussioncontrasting

confidence: 62%

MICU1 may be a promising intervention target for gut-derived sepsis induced by intra-abdominal hypertension

Leng

Zhao

et al. 2016

Cell Death Discovery

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“…This family is present in values lower than 1% in all other animals. However, its role here is difficult to determine due to the contradictory character assigned to this family in the literature, either as an actor in different pathologies [77,78] or as a keeper of the gut homeostasis [79,80].…”

Section: Discussionmentioning

confidence: 99%

A Diet Based on Cured Acorn Ham with Oleic Acid Content Promotes Anti-Inflammatory Gut Microbiota Shifts and Prevents Ulcerative Colitis in an Animal Model

Fernández¹,

Fuente²,

García³

et al. 2019

Preprint

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Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

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“…The scoring was performed independently by 3 dermatopathologists. The detailed scoring system was based on the reported literature (15).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

Wang¹,

Li²,

Zhang³

et al. 2019

Acta Derm Venerol

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SIGNIFICANCEIPA-3, a small molecular inhibitor of p21-activated kinase 1 (PAK1) phosphorylation, has anti-tumor activity in multiple cancers. However, its role in cutaneous T-cell lymphoma and the underlying molecular pathogenesis are still unclear. This study investigates the role of IPA-3 on cutaneous Tcell lymphoma cells. Pho-PAK1 overexpression is seen in patients with cutaneous T-cell lymphoma. IPA-3 treatment induces apoptosis and inhibits cell growth by inducing EGR1 expression and simultaneously down-regulating the levels of BCL-2 and pho-BAD. Therefore, pho-PAK1 may be a potential tumor marker and therapeutic target of cutaneous T-cell lymphoma.Cutaneous T-cell lymphoma (CTCL) represents a rare group of extranodal T-cell lymphoproliferative diseases. Due to poor clinical outcome of CTCL, there is an urgent need for new and improved therapies. A small molecule, IPA-3, which inhibits p21-activated kinase 1 (PAK1), has shown therapeutic potential in various types of malignancies. In the present study, the anti-tumor effect of IPA-3 and its underlying molecular mechanism was evaluated. High expression of phosphorylated-PAK1 (pho-PAK1) was seen in CTCL lesional skin compared to benign inflammatory dermatoses. IPA-3 could significantly inhibit the proliferation of 3 CTCL lines in a dose-and time-dependent manner. The percentage of apoptotic cells was higher in the treatment group. Further, IPA-3 treatment caused increased EGR1 protein levels and decreased apoptosis-related BCL-2 and pho-BAD protein levels. In summary, inhibition of pho-PAK1 has significant antitumor effects in CTCL cells and it can be explored as a future therapeutic option.

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Effects of acute intra-abdominal hypertension on multiple intestinal barrier functions in rats

Cited by 43 publications

References 53 publications

MICU1 may be a promising intervention target for gut-derived sepsis induced by intra-abdominal hypertension

MICU1 may be a promising intervention target for gut-derived sepsis induced by intra-abdominal hypertension

A Diet Based on Cured Acorn Ham with Oleic Acid Content Promotes Anti-Inflammatory Gut Microbiota Shifts and Prevents Ulcerative Colitis in an Animal Model

Targeting Phosphorylation of p21-activated Kinase 1 at Thr423 Induces Cell Cycle Arrest and Apoptosis in Cutaneous T-cell Lymphoma Cells

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