Xylosyltransferase 2 deficiency and organ homeostasis.

In this paper we characterize the function of Xylosyltransferase 2 (XylT2) in different tissues to investigate the role XylT2 has in the proteoglycan (PG) biochemistry of multiple organs. The results show that in all organs examined there is a widespread and significant decrease in total XylT activity in Xylt2 knock out mice (Xylt2-/-). This decrease results in increased organ weight differences in lung, heart, and spleen. These findings, in addition to our previous findings of increased liver and kidney weight with loss of serum XylT activity, suggest systemic changes in organ function due to loss of XylT2 activity. The Xylt2-/- mice have splenomegaly due to enlargement of the red pulp area and enhanced pulmonary response to bacterial liposaccharide. Tissue glycosaminoglycan composition changes are also found. These results demonstrate a role of XylT2 activity in multiple organs and their PG content. Because the residual XylT activity in the Xylt2-/- is due to xylosyltransferase 1 (XylT1), these studies indicate that both XylT1 and XylT2 have important roles in PG biosynthesis and organ homeostasis.

Lung and general health effects of Toll-like receptor-4 (TLR4)-interacting SPA4 peptide.

BACKGROUND: A surfactant protein-A-derived peptide, which we call SPA4 peptide (amino acids: GDFRYSDGTPVNYTNWYRGE), alleviates lung infection and inflammation. This study investigated the effects of intratracheally administered SPA4 peptide on systemic, lung, and health parameters in an outbred mouse strain, and in an intratracheal lipopolysaccharide (LPS) challenge model. METHODS: The outbred CD-1 mice were intratracheally administered with incremental doses of SPA4 peptide (0.625-10 µg/g body weight) once every 24 h, for 3 days. Mice left untreated and those treated with vehicle were included as controls. Mice were euthanized after 24 h of last administration of SPA4 peptide. In order to assess the biological activity of SPA4 peptide, C57BL6 mice were intratracheally challenged with 5 µg LPS/g body weight and treated with 50 µg SPA4 peptide via intratracheal route 1 h post LPS-challenge. Mice were euthanized after 4 h of LPS challenge. Signs of sickness and body weights were regularly monitored. At the time of necropsy, blood and major organs were harvested. Blood gas and electrolytes, serum biochemical profiles and SPA4 peptide-specific immunoglobulin G (IgG) antibody levels, and common lung injury markers (levels of total protein, albumin, and lactate, lactate dehydrogenase activity, and lung wet/dry weight ratios) were determined. Lung, liver, spleen, kidney, heart, and intestine were examined histologically. Differences in measured parameters were analyzed among study groups by analysis of variance test. RESULTS: The results demonstrated no signs of sickness or changes in body weight over 3 days of treatment with various doses of SPA4 peptide. It did not induce any major toxicity or IgG antibody response to SPA4 peptide. The SPA4 peptide treatment also did not affect blood gas, electrolytes, or serum biochemistry. There was no evidence of injury to the tissues and organs. However, the SPA4 peptide suppressed the LPS-induced lung inflammation. CONCLUSIONS: These findings provide an initial toxicity profile of SPA4 peptide. Intratracheal administration of escalating doses of SPA4 peptide does not induce any significant toxicity at tissue and organ levels. However, treatment with a dose of 50 µg SPA4 peptide, comparable to 2.5 µg/g body weight, alleviates LPS-induced lung inflammation.

A Critical Role for P2X7 Receptor-Induced VCAM-1 Shedding and Neutrophil Infiltration during Acute Lung Injury.

Pulmonary neutrophils are the initial inflammatory cells that are recruited during lung injury and are crucial for innate immunity. However, pathological recruitment of neutrophils results in lung injury. The objective of this study is to determine whether the novel neutrophil chemoattractant, soluble VCAM-1 (sVCAM-1), recruits pathological levels of neutrophils to injury sites and amplifies lung inflammation during acute lung injury. The mice with P2X7 receptor deficiency, or treated with a P2X7 receptor inhibitor or anti-VCAM-1 Abs, were subjected to a clinically relevant two-hit LPS and mechanical ventilation-induced acute lung injury. Neutrophil infiltration and lung inflammation were measured. Neutrophil chemotactic activities were determined by a chemotaxis assay. VCAM-1 shedding and signaling pathways were assessed in isolated lung epithelial cells. Ab neutralization of sVCAM-1 or deficiency or antagonism of P2X7R reduced neutrophil infiltration and proinflammatory cytokine levels. The ligands for sVCAM-1 were increased during acute lung injury. sVCAM-1 had neutrophil chemotactic activities and activated alveolar macrophages. VCAM-1 is released into the alveolar airspace from alveolar epithelial type I cells through P2X7 receptor-mediated activation of the metalloproteinase ADAM-17. In conclusion, sVCAM-1 is a novel chemoattractant for neutrophils and an activator for alveolar macrophages. Targeting sVCAM-1 provides a therapeutic intervention that could block pathological neutrophil recruitment, without interfering with the physiological recruitment of neutrophils, thus avoiding the impairment of host defenses.

Percutaneous single-fiber reflectance spectroscopy of canine intervertebral disc: is there a potential for in situ probing of mineral degeneration?

BACKGROUND AND OBJECTIVES: Intervertebral disc herniation is a common disease in chondrodystrophic dogs, and a similar neurologic condition also occurs in humans. Percutaneous laser disc ablation (PLDA) is a minimally invasive procedure used increasingly for prevention of disc herniation. Currently, PLDA is performed on thoracolumbar discs with the same laser energy applied regardless of the differing extent of degeneration among mineralized discs. In a previous study performed on 15 normal and 6 degenerated intervertebral discs in chondrodystrophoid canine species, it was demonstrated that percutaneous single-fiber reflectance spectroscopy (SfRS) detected increased light scattering from mineralized intervertebral discs when comparing to normal discs. The objective of this study is to evaluate how SfRS evaluation of mineralized discs in situ fairs with X-ray radiography and computed tomography (CT) diagnoses and if SfRS sensing of the scattering changes correlates with the level of mineral degeneration in nucleus pulposus. MATERIALS AND METHODS: Percutaneous SfRS was performed on a total of 28 intervertebral discs of three dogs post-mortem, through a 20 gauge spinal needle standard to PLDA. The raw SfRS measurement was normalized to extract a dimension-less spectral intensity profile, from which the average over 600-900 nm was used as the SfRS intensity index to compare among the measured discs. The discs were imaged prior to percutaneous SfRS by radiography and CT, and harvested after percutaneous SfRS for histopathologic examinations. RESULTS: Five among 10 discs of dog #1, six among 9 discs of dog #2, and nine out of 9 discs of dog #3 were determined by histopathology to have central focal or multi-focal areas of mineralization occupying 5-75% of the examined area of nucleus pulposus. The overall numbers of discs with detectable and undetectable central mineralization were 20 and 8, respectively. CT resulted in one false positive (FP) and four false negative (FN) diagnoses for dog #1, three FP and zero FN diagnoses for dog #2, and zero FP and one FN diagnosis for dog #3. Of the total 28 discs the CT had an overall positive predictive value (PPV) of 78.8% and an overall negative predictive value (NPV) of 44.4%. X-ray radiography gave five FN diagnoses for dog #1, two FN diagnoses for dog #2, and eight FN diagnoses for dog #3. Of the total 28 discs the radiography had an overall PPV of 100% and an overall NPV of 30.4%. The receiver-operating-characteristic analysis of the SfRS measurement was performed on 24 discs that had a central mineralization not greater than 50%. An area-under-curve of 0.6758 infers that the SfRS intensity weakly indicates the level of mineralization. CONCLUSIONS: Percutaneous SfRS may be useful as an in situ sensing tool for assessing the level of mineral degeneration in intervertebral discs for the prospect of disc-specific dosage adjustment in PLDA.

Identification of microRNAs changed in the neonatal lungs in response to hyperoxia exposure.

Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease of premature infants. BPD can be attributed to the dysregulation of normal lung development due to ventilation and oxygen toxicity, resulting in pathologic complications of impaired alveolarization and vascularization. MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression posttranscriptionally and are implicated in diverse biological processes and diseases. The objectives of this study are to identify the changed miRNAs and their target genes in neonatal rat lungs in response to hyperoxia exposure. Using miRNA microarray and real-time PCR analyses, we found downregulation of five miRNAs, miR-342, miR-335, miR-150, miR-126*, and miR-151*, and upregulation of two miRNAs, miR-21 and miR-34a. Some of these miRNAs had the highest expression during embryonic and early postnatal development. DNA microarray analysis yielded several genes with conserved binding sites for these altered miRNAs. Glycoprotein nonmetastatic melanoma protein b (GPNMB) was experimentally verified as a target of miR-150. In summary, we identified seven miRNAs that were changed in hyperoxia-exposed neonatal lungs. These results provide a basis for deciphering the mechanisms involved in the spatial and temporal regulation of proteins that contribute to the pathogenesis of BPD.

Effective Prophylactic Therapy for Exposure to Monkey B Virus (Macacine alphaherpesvirus 1).

Zoonotic monkey B virus (Macacine alphaherpesvirus 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system. To test this hypothesis, the efficacy of topical administration of several drugs against lethal BV infection was evaluated in female BALB/c mice that were infected by scarification. Drugs were then applied to the site of inoculation. As 3% preparations, most drugs were only minimally effective or ineffective. In contrast, ganciclovir and cidofovir were very effective. The ED50 for cidofovir was 0.007%, compared with 1.1% for ganciclovir. At 0.5%, cidofovir protected against both death and neurologic signs, whereas 5% ganciclovir only protected against death but not neurologic involvement. All genotypes of BV were equally susceptible to cidofovir and ganciclovir. For maximal effectiveness, treatment with both cidofovir and ganciclovir had to be initiated within 8 h of infection. Cidofovir was completely protective when administered only on the day of infection, whereas a minimum of 5 d of treatment was required for maximal ganciclovir efficacy. These studies showed that topical cidofovir treatment started soon after BV exposure was very effective in preventing BV from invading the nervous system, whereas ganciclovir treatment was only partially effective. In addition, cidofovir was protective against a ganciclovir-resistant BV mutant, whereas ganciclovir was not. These studies showed that topical cidofovir treatment started soon after BV exposure is more effective than ganciclovir in preventing BV from invading the CNS.

Light and transmission electron microscopic characteristics of a novel Hepatozoon spp. in naturally infected cotton rats (Sigmodon hispidus).

A novel species of Hepatozoon was recently reported in cotton rats (Sigmodon hispidus) collected from an area of Oklahoma where American canine hepatozoonosis is endemic. In this study, the various stages of merogony of the parasite were characterized by light and electron microscopy. Meronts occurred within parasitophorous vacuoles in hepatocytes and ranged from mononucleated spherical forms to large, mature forms in vacuoles that contained approximately 50 peripherally arranged merozoites. Developing merozoites had characteristic apicomplexan organelles, including anterior and posterior polar rings, a conoid, microtubules, rhoptries, micronemes, and a trilaminar membrane. As the meronts matured, numerous curvilinear merozoites budded from a residual body. This morphologic characterization extends our understanding of this novel Hepatozoon and adds information about the hepatozoa, apicomplexan parasites that infect numerous species.

Experimental transmission of Hepatozoon americanum to rodents.

Laboratory-raised cotton rats (Sigmodon hispidus), outbred white mice (Mus musculus), and C57BL/6J-Lystbg-J/J mice (M. musculus) that were administered approximately 50 sporulated oocysts of Hepatozoon americanum (AF176836) by gavage developed inflammatory lesions containing parasitic cystozoites in cardiac and skeletal muscle, kidney, and lung. Sprague-Dawley rats (Rattus norvegicus) similarly exposed showed no evidence of infection. Cystozoites were first detected by histopathologic examination four weeks after exposure to oocysts. Globular, PAS-positive material accumulated around the cystozoites as the duration of infection lengthened. Nested PCR analysis of tissues collected 16 weeks post-exposure was positive for the 18S rRNA Hepatozoon sp. gene and the DNA sequence of the fragment amplified was 99.6% and 99.8% identical to H. americanum sequences previously reported from naturally-infected dogs (AF176836 and AY864676, respectively). Merogonous and gamontogonous stages of the parasite were not detected in any of the cystozoite-infected rodents.

Clinical observations, biochemical data, and postmortem and histopathologic findings in young dairy calves fed zeolite clinoptilolite binder combined with milk replacer.

OBJECTIVE: To identify any adverse effects on health or performance in young dairy calves fed clinoptilolite mixed with milk replacer. ANIMALS: 26 male Holstein calves (1 to 7 days old). PROCEDURES: Twice daily for 28 days, calves were fed milk replacer with no clinoptilolite (control group; n=8), 0.5% clinoptilolite (low-dosage group; 9), or 2% clinoptilolite (high-dosage group; 9); each calf consumed approximately 12% of its body weight (based on the replacer solids in the milk replacer mixture)/d. For each calf, subjective health assessments, weight and rectal temperature measurements, and CBC and serum biochemical analyses were performed at intervals. All calves underwent necropsy. RESULTS: 2 calves were euthanized during the experiment because of bronchopneumonia or enteritis. Body weight and average daily gain did not differ among treatment groups. The percentage of monocytes and serum total protein concentration in the low-dosage group were higher than values in the control and high-dosage groups. Compared with values for either clinoptilolite-treated group, BUN concentration was greater in the control group. Serum globulin concentration differed significantly among groups (2.77, 2.50, and 2.36 g/dL in the low-dosage, control, and high-dosage groups, respectively). At necropsy, gross lesions associated with clinoptilolite treatment were not detected in any of the calves. CONCLUSIONS AND CLINICAL RELEVANCE: Even under stressful conditions, clinoptilolite fed at low or high dosages did not affect the performance of dairy calves and had no negative effect on WBC count and blood metabolite concentrations and enzyme activities. Clinoptilolite ingestion was not associated with treatment-specific gross changes.

Dendritic cell leukemia in a Golden Retriever.

An 8-year-old castrated male Golden Retriever was evaluated for decreased appetite, lethargy, and labored breathing of 1-week duration. Bilateral pulmonary infiltrates, hepatomegaly, and splenomegaly were present. Results of a CBC revealed marked leukocytosis (62,600/microL; reference interval 4000-15,500/microL) and large numbers of atypical cells (30,700/microL) with abundant cytoplasm. There was no concurrent anemia, neutropenia, or thrombocytopenia. Morphology of the atypical cells was most consistent with a histiocytic origin. Similar cells were identified in bone marrow aspirates, and were morphologically suggestive of the macrophage variant of disseminated histiocytic sarcoma. However, flow cytometry of the abnormal circulating cells revealed CD1c, CD11c, and major histocompatibility complex (MHC) Class II expression without expression of CD11d or lymphoid markers, consistent with myeloid dendritic antigen-presenting cells. At necropsy, the splenic architecture was effaced by neoplastic histiocytes that were also infiltrating lung, liver, an abdominal lymph node, myocardium, an bone marrow. Immunohistochemistry of the splenic neoplastic cells confirmed dendritic cell origin (CD1c+, CD11c+, MHC II+, no expression of CD11d and lymphoid markers). To the authors' knowledge, this is the first report of canine dendritic cell leukemia-in this instance accompanied by marked tissue infiltration.

Metastatic disease in a dog with a well-differentiated perianal gland tumor.

Fine-needle aspirates from a perianal mass on an 8-year-old, intact male, Miniature Poodle presenting for tenesmus showed a uniform population of well-differentiated hepatoid cells with no notable criteria of malignancy. The cytologic diagnosis was a perianal gland tumor, with adenoma likely given the cytomorphology. The abdominal ultrasound revealed multiple, markedly enlarged, intra-abdominal lymph nodes. LN aspirates also showed well-differentiated polygonal, hepatoid cells displaying no notable cellular atypia. The presence of the metastasis led to the interpretation of a well-differentiated, malignant perianal gland tumor despite the benign cellular appearance. Histopathology of the surgically excised perianal mass and one enlarged abdominal lymph node revealed lobules of uniform polygonal hepatoid cells arranged in organized islands and trabeculae surrounded by a single layer of uniform reserve cells. Few mitotic figures were present. The only histopathologic indication of malignancy within the primary mass was the presence of small islands of well-differentiated hepatoid cells infiltrating into adjacent tissue and possible lymphatic invasion. The histopathologic diagnosis was perianal gland adenocarcinoma. Most textbooks describe perianal gland adenocarcinomas as showing increased cellular atypia including pleomorphism, disorganization of hepatoid cells, and increased numbers of pleomorphic reserve cells with mitotic figures. This case is an example of the occurrence of a well-differentiated perianal gland tumor with metastasis and highlights the importance of realizing that with these tumors, a benign cytologic and histologic appearance may not correlate with biologic behavior. To the authors' knowledge, this is the first case reporting both the cytologic and histologic appearance of a well-differentiated metastatic hepatoid gland tumor.

Congenital amelanotic melanoma in a crossbred heifer calf.

A large, pedunculated cutaneous mass protruding from the left flank fold and an enlarged left prefemoral lymph node were found on examination of a 3-d-old crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral lymphadenopathy, and the mass, along with the left prefemoral lymph node, was surgically excised. Histologic examination of the mass and the lymph node revealed a homogeneous population of neoplastic cells that stained positively with immunohistochemical stains S100 and melan A, supporting a diagnosis of congenital amelanotic melanoma with nodal metastasis. Two months later, the calf became acutely recumbent and was euthanized after clinical examination revealed widespread metastasis. Gross autopsy revealed widely disseminated metastases that involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa, multiple lymph nodes, and the marrow cavity of several long bones. Our case serves as a reminder that, although rare, congenital neoplasms occur in bovids and have the potential for aggressive, metastatic behavior.

Concurrent multiple myeloma and mast cell neoplasia in a 13-year-old castrated male Maine Coon cat.

A 13-year-old, castrated male Maine Coon cat was presented to Oklahoma State University Boren Veterinary Medical Teaching Hospital for yearly echocardiographic examination monitoring hypertrophic cardiomyopathy (HCM) diagnosed in 2003. Physical examination revealed a heart murmur and premature beats, likely related to HCM, but was otherwise unremarkable. A biochemistry profile revealed a hyperglobulinemia (6.3 g/dL). Cytologic examination of fine-needle aspirates from liver and spleen revealed increased numbers of plasma cells and mast cells, confirmed with subsequent histologic examination. Immunohistochemistry (IHC) for c-kit in the spleen and liver showed mast cells predominantly exhibiting type I staining pattern, with moderate numbers exhibiting type II pattern in spleen, and scattered cells exhibiting type II and III patterns in liver. Bone marrow cytology and core biopsy documented approximately 22% plasma cells. Cutaneous masses on the cat's left shoulder and right carpus were cytologically confirmed mast cell tumors. Serum protein electrophoresis with immunofixation confirmed an IgG monoclonal gammopathy. This is an example of 2 hematologic neoplasms occurring simultaneously in a cat. Concurrent pathologies may be overlooked if a single disease is diagnosed and suspected of causing all clinical signs. Both neoplasms were well differentiated, and neoplastic cells could have easily been interpreted as a reactive population had a full workup not been performed. Missing either diagnosis could result in a potentially lethal outcome. Eleven months after diagnoses, the cat was clinically doing well following a splenectomy and oral prednisolone and chlorambucil chemotherapy. Globulins decreased to 4.9 g/dL.

Thyroglossal Duct Carcinoma in a Cat.

A 14 yr old castrated domestic shorthair cat presented for a fluid-filled structure in the ventral cervical region that had been present for 1 yr and had not resolved after repeated aspiration and drainage. Cervical computed tomography showed an approximately 10 cm, fluid-filled, multilobulated mass located on the ventrolateral right side of the cervical region extending into the thoracic inlet. Cytologic examination of the fluid revealed cystic fluid with evidence of chronic hemorrhage. The mass was surgically removed, and histopathologic examination revealed a thyroglossal duct carcinoma. Thyroid and parathyroid gland origin were ruled out by negative immunohistochemical staining for thyroglobulin, parathyroid hormone, calcitonin, and synaptophysin. No adjunctive treatment was performed and no recurrence was noted at 14 mo. Thyroglossal duct carcinoma has not been previously reported in a cat. There are two previous reports of squamous cell carcinoma of the thyroglossal duct in dogs. In humans, with complete removal and no evidence of metastasis, carcinoma of the thyroglossal duct has a good prognosis for recovery.

Efficacy of Bdellovibrio bacteriovorus 109J for the treatment of dairy calves with experimentally induced infectious bovine keratoconjunctivitis.

OBJECTIVE To determine the efficacy of Bdellovibrio bacteriovorus 109J for the treatment of calves with experimentally induced infectious bovine keratoconjunctivitis (IBK). ANIMALS 12 healthy dairy calves. PROCEDURES For each calf, a grid keratotomy was performed on both eyes immediately before inoculation with Moraxella bovis hemolytic strain Epp63-300 (n = 11 calves) or nonhemolytic strain 12040577 (1 calf). For each calf inoculated with M bovis Epp63-300, the eyes were randomly assigned to receive an artificial tear solution with (treatment group) or without (control group) lyophilized B bacteriovorus 109J. Six doses of the assigned treatment (0.2 mL/eye, topically, q 48 h) were administered to each eye. On nontreatment days, eyes were assessed and corneal swab specimens and tear samples were collected for bacterial culture. Calves were euthanized 12 days after M bovis inoculation. The eyes were harvested for gross and histologic evaluation and bacterial culture. RESULTS The calf inoculated with M bovis 12040577 did not develop corneal ulcers. Of the 22 eyes inoculated with M bovis Epp63-300, 18 developed corneal ulcers consistent with IBK within 48 hours after inoculation; 4 of those eyes developed secondary corneal ulcers that were not consistent with IBK. Corneal ulcer size and severity and the time required for ulcer healing did not differ between the treatment and control groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that B bacteriovorus 109J was not effective for the treatment of IBK; however, the experimental model used produced lesions that did not completely mimic naturally occurring IBK.

Honey mesquite toxicosis in a goat.

Honey mesquite (Prosopis glandulosa) is distributed across a large portion of the southwestern United States. Ingestion of young leaves, pods, or beans can cause toxicosis in cattle and goats if they comprise a substantial portion of their diet. Goats, as browsers, are most likely to develolp mesquite toxicosis. Sheep appear to be more resistant to the plant's toxic effects. Consistent clinical signs include weight loss, ptyalism, mandibular tremors, tongue protrusion, and dysphagia. Diagnosis of mesquite toxicosis is largely made on the basis of history and clinical signs with exclusion of appropriate differentials. Laboratory findings are nonspecific but may reveal a mild anemia and hypoglycemia. Postmortem findings suggestive of mesquite toxicosis are limited to fine vacuolation of neurons in the trigeminal motor nucleus. Treatment consists of an alternative diet and supportive care. The disease is treatable in cattle and sheep but has a high case fatality rate in goats.

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial injury and extensive inflammation of the pulmonary parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling in ARDS provide insights into understanding of molecular mechanisms of the pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA interactions in a rat model of ARDS by combining miRNA and mRNA microarray analyses. METHODS: Rat model of ARDS was induced by saline lavage and mechanical ventilation. The expression profiles of both mRNAs and miRNAs in rat ARDS model were performed by microarray analyses. Microarray data were further verified by quantitative RT-PCR. Functional annotation on dys-regulated mRNAs and miRNAs was carried out by bioinformatics analysis. RESULTS: The expression of 27 miRNAs and 37 mRNAs were found to be significantly changed. The selected miRNAs and genes were further verified by quantitative real-time PCR. The down-regulated miRNAs included miR-24, miR-26a, miR-126, and Let-7a, b, c, f. The up-regulated miRNAs were composed of miR-344, miR-346, miR-99a, miR-127, miR-128b, miR-135b, and miR-30a/b. Gene ontology and functional annotation analyses indicated that up-regulated mRNAs, such as Apc, Timp1, and Sod2, were involved in the regulation of apoptosis. Bioinformatics analysis showed the inverse correlation of altered miRNAs with the expression of their predicted target mRNAs. While Sod2 was inversely correlated with Let-7a, b, c, f., Ebf1 and Apc were inversely correlated with miR-24 and miR-26a, respectively. miR-26a, miR-346, miR-135b, miR-30a/b, miR-344, and miR-18a targeted multiple altered mRNAs. Gabrb1, Sod2, Eif2ak1, Fbln5, and Tspan8 were targeted by multiple altered miRNAs. CONCLUSION: The expressions of miRNAs and mRNAs were altered in a rat model of ARDS. The identified miRNA-mRNA pairs may play critical roles in the pathogenesis of ARDS.