A tale of two niches: differential functions for VCAM-1 in satellite cells under basal and injured conditions
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Authors: Choo, Hyo-Jung; Canner, James P.; Vest, Katherine E.; Thompson, Zachary; Pavlath, Grace K.
Abstract
Cell-cell adhesion molecules play key roles in maintaining quiescence or promoting activation of various stem cells in their niche. Muscle stem cells called satellite cells (SC) are critical for skeletal muscle regeneration after injury, but little is known about the role of adhesion molecules in regulating the behavior of these stem cells. Vascular cell adhesion molecule-1(VCAM-1) is a cell-cell adhesion protein expressed on quiescent and activated SC whose function is unknown in this context. We deleted Vcam1 from SC using an inducible Cre recombinase in young mice. In the injured niche, Vcam 1(-/-) SC underwent premature lineage progression to a more differentiated state as well as apoptosis leading to a transient delay in myofiber growth during regeneration. Apoptosis was also increased in Vcam 1(-/-) SC in vitro concomitant with decreased levels of phosphorylated Akt, a prosurvival signal activated by VCAM-1 signaling in other cell types. During muscle regeneration, we observed an influx of immune cells expressing alpha 4 integrin, a component of the major, high-affinity VCAM-1 ligand, alpha 4 beta 1 integrin. Furthermore, alpha 4 integrin mRNA and protein were induced in SC 2 days after injury. These results suggest that SC interact with other SC as well as immune cells through alpha 4 beta 1 integrin in the injured niche to promote expansion of SC. In the uninjured niche, multiple cell types also expressed alpha 4 integrin. However, only basal fusion of Vcam 1(-/-) SC with myofibers was decreased, contributing to decreased myofiber growth. These studies define differential roles for VCAM-1 in SC depending on the state of their niche.
Anti-inflammation effects of the total saponin fraction fromDioscorea nipponicaMakino on rats with gouty arthritis by influencing MAPK signalling pathway
BMC COMPLEMENTARY MEDICINE AND THERAPIES
Authors: Zhou, Qi; Sun, Hui Juan; Liu, Shu Min; Jiang, Xi Hong; Wang, Qiu Yue; Zhang, Shuang; Yu, Dong Hua
Abstract
Background Dioscorea nipponicaMakino is widely used in traditional Chinese medicine to treat gouty arthritis. Methods Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPAR gamma in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPAR gamma and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method. Results Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum. Conclusion RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.