BACKGROUND:Pericytes, which are widely distributed in the microvasculature except lymphatic vessels, are not only a constituent of microvessels, but also play an important role in microvascular occurrence, development, stability, maturity and remodeling. Its signal transduction is currently a hot spot. OBJECTIVE:To review recent advances in the signal pathways related to pericytes and angiogenesis. METHODS:We retrieved PubMed database, Wanfang database, CNKI database and China Biology Medicine disc for articles addressing pericytes and angiogenesis published from 1994 to 2014. The keywords were “pricytes; endothelial cels; microvessels; signal transduction” in English and Chinese, respectively.RESULTS AND CONCLUSION:In the early stage of capilary formation, recruitment of pericytes contributes to the occurrence and development of new blood capilaries. However, in the late stage of angiogenesis, pericytes inhibit endothelial cel proliferation and promote endothelial cel differentiation, thereby promoting vascular maturation, maintaining normal structure and regulating their permeability. In this process, signaling pathways of platelet-derived growth factor B/platelet-derived growth factor receptor β, transforming growth factor β, angiopoietin-1/Tie-2, human heparin binding epidermal growth factor/ErbBs, and stromal cel derived factor 1α/CXCR4 play an important regulatory role in pericytes and angiogenesis.

Periostin is a matri-cellular protein which was originally identified in MC3T3-E 1 osteoblast-like cell line,expressing in multiple tissues like bones,teeth,skin and cardiac valves.Periostin is also found in a large variety of cancers and injured tissues,involving in cancer cell invasion and metastasis as well as wound repair.Recent studies have suggested the role of Periostin in osteoblast adhesion and differentiation,fibrillogenesis,mineralization and bone fracture healing,and its expression is regulated by mechanical stress,various transcription factors,hormones and growth factors.In this article,we will discuss the expression,localization and general characteristics of Periostin,and provide a review on the study of it in bone biology.

Objective To examine whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation via mammalian target of rapamycin (mTOR) signaling.Methods The cell proliferation and cycle were determined by methylthiazoletetrazolium(MTT) assay and flow cytometry,respectively.The mRNA expression of AMP-activated protein kinase(AMPK) was detected by realtime PCR.The phosphorylation levels of protein kinase B (Akt),mTOR,eukaryotic translation initiation factor 4E binding protein 1 (4EBP1),and 70S6 kinase (p70S6K) were measured by Western blot.Results 0.25 mmol/L LA promoted high glucose-sitmulated rat mesangial cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),along with increased phosphorylation levels of Akt,mTOR,p70S6K,and 4EBP1 (P＜0.05).These effects of 0.25 mmol/L LA disappeared when Akt activity was inhibited.On the contrary,1.0 mmol/L LA inhibited high glucose-induced cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),with the decreased phosphorylation levels of mTOR,p70S6K,and 4EBP1 (P＜ 0.05) and the enhanced activity of AMPK(P＜0.01).These effects of 1.0 mmol/L LA were prevented when AMPK activity was inhibited.Conclusions LA dose-dependently regulates mesangial cell proliferation induced by glucose via mTOR signaling pathway.

Objective To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. Methods Synchronized HMCs were divided into following groups: (1) Normal glucose control group ( NG, 5. 5 mmol/L glucose) ;(2) High glucose group (HG, 30 mmol/L glucose) ; (3) Mannitol group (Man, 5.5 mmol/L glucose + 24. 5 mmol/L mannitol) ; (4) High glucose + fasudil group ( HG + F, the concentrations of fasudil were 25 ,50 and 100 μmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK- Ⅰ, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin ( FN) , CTGF, TNFα in the supernatant. Results ( 1) RhoA, ROCK- Ⅰand CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2) Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK- Ⅰ , CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. Conclusion Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.