RESUMEN
Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disorder with distinctive deposition of calcium phosphate microliths in the lungs. Mutation of the SLC34A2 gene was proved to be responsible for PAM. Here, we report the study of a family affected by PAM in China. Two daughters of an inbred family whose parents are cousins and are affected by PAM. Mutation analysis of the SLC34A2 gene by polymerase chain reaction (PCR) amplification and direct sequencing in both patients revealed that exon 5 was deleted on both alleles. Both parents of the patients are proved to be carriers of the mutated allele. Gap-PCR was performed to determine the breakpoints and a homologous deletion of 1152 bp encompassing exon 5 of the SLC34A2 gene (c.IVS4+1452_IVS5+660del) was confirmed. A 4-bp fragment of TGGG was located on the edge of both upstream and downstream breakpoints. The upstream breakpoint lies in the same region as the breakpoint of a fused gene SLC34A2-ROS1, which encodes a constitutive kinase in the lung cancer cell line HCC78 and nonsmall-cell lung cancer (NSCLC), suggesting that the deletion in this family is a hot spot for recombination, not only in cancer samples with somatic mutation, but also in PAM patients with germline genetic defects of SLC34A2.
Asunto(s)
Calcinosis/genética , Enfermedades Genéticas Congénitas/genética , Enfermedades Pulmonares/genética , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIb/genética , Pueblo Asiatico , Calcinosis/patología , Femenino , Enfermedades Genéticas Congénitas/patología , Humanos , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/patología , Masculino , Mutación , Proteínas de Fusión Oncogénica/genética , Linaje , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Eliminación de SecuenciaRESUMEN
AIM: To investigate the role of hydrogen sulfide (H_2S) in the cholecystokinin octapeptide (CCK-8) attenuating lipopolysaccharide (LPS)-induced lung injury. METHODS: A rat model of lung injury induced by intravenous injection of LPS was developed. Male Wistar rats were divided into normal control group, LPS group, LPS+CCK-8 group and CCK-8 group. Six hours after LPS injection, partial pressure of oxygen in the arterial blood (PaO_2), H_2S content and cystathionine-γ-lyase (CSE) activity in lung tissue were detected. The mRNA expression of CSE in lung tissue was determined by RT-PCR;the structure of lung tissues was observed under optical microscope. RESULTS: Compared to normal control rats, the LPS-treated rats had significantly decreased PaO_2 level, increased index of quantitative assessment (IQA) score, while H_2S content, CSE activity and the mRNA expression of CSE in lung tissue were significantly increased (all P<0.05). Administration of CCK-8 into LPS-treated rats increased the PaO_2 level and alleviated the degree of lung injury (measured by IQA score). In addition, CCK-8 decreased H_2S content, CSE activity, and the mRNA expression of CSE (all P<0.05). No significant difference of the above-mentioned parameters between CCK-8 group and normal control group was observed. CONCLUSION: CCK-8 reduces LPS-induced lung injury through inhibiting the generation of endogenous H_2S.
