Role of Surfactant Proteins A and D in Sepsis-Induced Acute Kidney Injury

Liu, Jiao; Abdel-Razek, Osama; Li, Yong; Hu, Fengqi; Zhou, Qingshan; Cooney, Robert N.; Wang, Guirong

doi:10.1097/shk.0000000000000270

Cited by 48 publications

(47 citation statements)

References 35 publications

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“…Our previous study also found SP-A/D KO mice had higher basal level of autophagy in liver and a more pronounced inflammatory response to sepsis than WT mice 46,47 . Of interest, in the present study, we observed uninfected SP-A/D KO mice exhibit significant higher basal levels of p38 MAPK phosphorylation compared with uninfected WT mice.…”

Section: Discussionmentioning

confidence: 66%

Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

Ding

Zhang

et al. 2015

Innate Immun

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To investigate the effects of surfactant proteins A and D (SP-A, SP-D) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared to control, level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than infected WT mice 24 and 48 h post-infection. Basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher compared to WT mice. Phosphorylated-p38 level was elevated in the kidney of WT mice post-infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI.

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Section: Discussionmentioning

confidence: 66%

Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

Ding

Zhang

et al. 2015

Innate Immun

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“…11 In addition, SP-A and SP-D attenuate kidney injury by modulating inflammation and apoptosis in sepsis-induced acute kidney injury 12 . However, whether or not SP-A plays a role in the process of non-infectious renal diseases, especially the chronic kidney diseases, the major cause of renal failure, remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Surfactant protein A deficiency exacerbates renal interstitial fibrosis following obstructive injury in mice

Tian

Ran

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Renal interstitial fibrosis is an inevitable consequence of virtually every type of chronic kidney disease. The underlying mechanisms, however, are not completely understood. In the present study, we identified surfactant protein A (SP-A) as a novel protein factor involved in the renal fibrosis induced by unilateral ureter obstruction (UUO). UUO induced SP-A expression in mouse kidney epithelium, likely due to the increased acidic stress and inflammation. Interestingly, SP-A deficiency aggravated UUO-prompted kidney structural damage, macrophage accumulation, and tubulointerstitial fibrosis. SP-A deficiency appeared to worsen the fibrosis by enhancing interstitial myofibroblast accumulation. Moreover, SP-A deficiency increased the expression of TGF-β1, the major regulator of kidney fibrosis, particularly in the interstitial cells. Mechanistically, SP-A deficiency increased the expression and release of high mobility group box 1 (HMGB1), a factor regulating TGF-β expression/signaling and implicated in renal fibrosis. SP-A also blocked HMGB1 activities in inducing TGF-β1 expression and myofibroblast transdifferentiation from kidney fibroblasts, demonstrating that SP-A protects kidney by impeding both the expression and fibrogenic function of HMGB1. Since SP-A physically interacted with HMGB1 both in vitro and in kidney tissue in vivo, SP-A may exert its protective role by binding to HMGB1 and thus titrating its activity during UUO-induced renal fibrosis.

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“…Apoptotic cells were detected by means of a deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) kit (Roche, Indianapolis, IN) according to the manufacturer’s instructions. Cell apoptosis was quantified by counting the number of TUNEL-positive cells in 20 random fields at ×400 magnification (20). …”

Section: Methodsmentioning

confidence: 99%

“…Frozen lungs were homogenized in RIPA buffer containing a cocktail of protease- and phosphatase-inhibitors (Roche), and the supernatants were used for Western blot analysis (20). Total protein concentrations of samples (lungs and BALF) were determined using the BCA micro assay kit (Thermo Scientific, Rockford, IL).…”

Section: Methodsmentioning

confidence: 99%

“…After that, the blot was blocked in 5% non-fat milk of Tris-buffered saline, and detected using a primary antibody against NF-κB (1:400, Santa Cruz Biotech), Caspase-3 (1:400, Santa Cruz Biotech), and Bcl-2 (1:400, Santa Cruz Biotech), as well as a anti-SP-B antibody (1:2000, Hycult biotech, Plymouth Meeting, PA). Thereafter, an anti-rabbit secondary antibody conjugated with horseradish peroxidase was applied (20). To standardize each protein in the blot, the blot was stripped and reprobed with β-Actin anti-body (1:400, Santa Cruz Biotech).…”

Section: Methodsmentioning

confidence: 99%

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Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

Abdel-Razek

et al. 2016

Shock

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Staphylococcus aureus is a common cause of nosocomial pneumonia frequently resulting in acute respiratory distress syndrome (ARDS). Surfactant protein B (SP-B) gene expresses two proteins involved in lowering surface tension and host defense. Genotyping studies demonstrate a significant association between human SP-B genetic variants and ARDS. Curcumins have been shown to attenuate host inflammation in many sepsis models. Our hypothesis is that functional differences of SP-B variants and treatment with curcumin (CMC2.24) modulate lung injury in bacterial pneumonia. Humanized transgenic mice, expressing either SP-B T or C allele without mouse SP-B gene, were used. Bioluminescent labeled S. aureus Xen36 (50 μl) was injected intratracheally to cause pneumonia. Infected mice received daily CMC2.24 (40 mg/kg) or vehicle alone by oral gavage. Dynamic changes of bacteria were monitored using in vivo imaging system. Histological, cellular and molecular indices of lung injury were studied in infected mice 48h after infection. In vivo imaging analysis revealed total flux (bacterial number) was higher in the lung of infected SP-B-C mice compared to infected SP-B-T mice (p<0.05). Infected SP-B-C mice demonstrated increased mortality, lung injury, apoptosis and NF-κB expression compared to infected SP-B-T mice. Compared to controls, CMC2.24 treatment significantly reduced the following: mortality, total bacterial flux and lung tissue apoptosis, inflammatory cells, NF-κB expression (p<0.05), and MMPs-2, -9, -12 activities (p<0.05). We conclude that mice with SP-B-C allele are more susceptible to S. aureus pneumonia than mice with SP-B-T allele; and that CMC2.24 attenuates lung injury thus reducing mortality.

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Role of Surfactant Proteins A and D in Sepsis-Induced Acute Kidney Injury

Cited by 48 publications

References 35 publications

Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

Surfactant protein A deficiency exacerbates renal interstitial fibrosis following obstructive injury in mice

Differential Susceptibility of Human Sp-B Genetic Variants on Lung Injury Caused by Bacterial Pneumonia and the Effect of a Chemically Modified Curcumin

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