MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12.

OBJECTIVE: To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma. METHODS: The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry. RESULTS: MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice. CONCLUSION: MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.

An SNP of the ZBTB38 gene is associated with idiopathic short stature in the Chinese Han population.

OBJECTIVE: Idiopathic short stature (ISS) refers to extreme short stature without any diagnostic explanation. Recently, three genome-wide association studies discovered associations between the ZBTB38 and adult height in different populations. Therefore, variations in the ZBTB38 might contribute to ISS. Furthermore, one study in Korean population showed that ZBTB38 gene was significantly associated with adult height, but not with ISS. We want to examine whether the variants in ZBTB38 are associated with ISS in Chinese Han. METHODS: A case-control association study was performed in 268 ISS patients and 513 healthy controls from Chinese Han population. Fourteen tag SNPs were selected and genotyped using SNaPshot method. Furthermore, expression of mRNA was quantified by RT-qPCR, and assessment of allelic expression imbalance was conducted with SNaPshot method. RESULTS: Seven ZBTB38 SNPs were significantly associated with ISS by allele tests (rs724016, rs1582874, rs11919556, rs6440006, rs7612543, rs62282002, rs18651435). And five loci were associated with ISS according to genotype (rs11919556, rs16851419, rs6440006, rs62282002, rs18651435). Notably, after applying the stringent Bonferroni correction for multiple testing, one SNP, rs16851435, remained significantly associated by allele and genotype (P = 5·30 × 10⁻4 for allele and P = 0·002 for genotype). Furthermore, the rs16851435 alleles were investigated association with ZTBT38 mRNA expression levels. The G allele showed a higher transcriptional activity than the T allele (P = 0·002). CONCLUSIONS: Our study indicated that the nonsynonymous SNP (rs16851435:T > G,p.Ser319Ala) of ZBTB38 was contributed to susceptibility of ISS in the Chinese Han population.