Hair regeneration in mice was promoted by 3-methyladenine through inhibiting autophagy flux / 中国药科大学学报

@#To explore the role of autophagy in hair follicle cycle and whether 3-methyladenine(3-MA)could promote hair regeneration in C57BL/6 mice through inhibiting autophagy flux, hair regeneration model of C57BL/6 mice was induced on the dorsal skin by depilation, and 3-MA was intraperitoneally injected to investigate hair regrowth, meanwhile vehicle and rapamycin(RAPA)were used as the controls. Results showed that 3-MA could obviously promote hair regrowth in depilated C57BL/6 mice. Furtherly, haematoxylin-eosin staining, immunohistochemical staining, immunofluorescence and Western blot tests were used to investigate the autophagy signals and the cell proliferation. Results showed that the expression of Beclin1 and LC3B II/I ratio were significantly decreased. Expression of P62 and Ki67 were increased, as well as the CD34 and CD49f double-labeled hair follicle stem cells were obviously increased inside bulge areas in 3-MA group, while contrarily in RAPA group. These results affirmed 3-MA, an autophagy inhibitor, could promote hair regeneration in depilated C57BL/6 mice by facilitating the transformation of hair follicle from telogen to anagen. 3-MA and other analogous autophagy inhibitors probably have a potential usage in future therapy in human telogen effluvium diseases.

Rapamycin reverse lipopolysaccharide-induced acute lung injury through acti-vating autophagy flux / 中国药科大学学报

This study was designed to examine the effects of autophagy on the lipopolysaccharide(LPS)-induced acute lung injury (ALI)and to analyze the possible mechanism.Kunming mice of clean grade were randomly divided into 6 groups:control group(saline;ip);model group(LPS 10 mg/kg;ip);RAP group(rapamycin 6 mg/kg;ip);RAP+LPS group (RAP 6 mg/kg and LPS 10 mg/kg;ip);3-MA group (3-methyladenine 300 μg/kg;ip);and 3-MA+LPS group (3-MA 300 μg/kg and LPS 10 mg/kg;ip).6 h after LPS injection;mortality was checked.Neutrophil aggregation;and the expressions of TNF-α;LC3 and P62 in lung tissue were checked by fluo-rescence microscopy and Western blot.The results revealed a higher mortality;neutrophil infiltration and TNF-αexpression and significantly increased levels of autophagy marker LC3-II and P62 in LPS group;in RAP+LPS group;pretreatment with RAP notably reversed LPS-induced neutrophil infiltration and TNF-αexpression;LC3-II were further slightly increased;while P62 was significantly decreased;in 3-MA+LPS group;pretreatment of 3-MA slightly decreased LC3-II expression;P62;neutrophil infiltration and TNF-αremained almost the same to those in LPS group.These data suggesed that;in sepsis;autophagy flux in the lung tissue is partially blocked;and RAP help to alleviate LPS-induced lung injury;which might through promoting autophagosome maturation;smoothing autophagy flux;and eventually to mitigate pulmonary inflammation.