近日上海交通大學生命科學技術學院力學生物學與醫(yī)學工程研究所在國家自然科學基金重點項目“血管細胞分化與遷移的力學生物學機制”研究取得重要進展,，研究論文發(fā)表在本年1月18日的《美國科學院院刊》（PNAS）上,。
這一研究項目是由上海交大的姜宗來教授主持的,，項目組的齊穎新副研究員為論文的第一作者,。姜宗來教授是改革開放以來我國自己培養(yǎng)的第一批醫(yī)學碩士和醫(yī)學博士,。九十年代初留學美國,，師從“現代生物力學之父”,、美國國家科學院院士,、國家工程院院士,、國家醫(yī)學科學院院士,、中國科學院首批外籍院士Y. C. Fung（馮元楨）教授,。1993年學成歸國，由于其在生物力學領域的杰出成就,，2004年獲得國務院政府特殊津貼,，并在2010年8月新加坡召開的第六屆世界生物力學大會上當選為世界生物力學理事會理事。
動脈粥樣硬化易發(fā)生在呈現血流擾動和低切應力的血管彎曲和分叉區(qū)域,。探討低切應力如何誘導血管重建（remodeling）,，進而導致動脈粥樣硬化的力學生物學（mechanobiology）機制是心血管研究的重要科學問題。
該論文應用差異血管蛋白質組學,、生物信息學和分子生物學技術相結合的方法,，在組織水平和細胞分子水平對低切應力影響血管壁細胞功能的機制進行了研究。結果表明,，低切應力直接作用于血管內皮細胞,，增加其合成、釋放血小板源性生長因子（PDGF-BB）和轉化生長因子β1（TGFβ1）,，而增加的PDGF-BB和TGFβ1具有不同生物功能,。血管內皮細胞釋放的PDGF-BB參與了內皮細胞自身增殖、遷移以及細胞內多種信號轉導分子的調控,；同時,，通過旁分泌作用調節(jié)與其相鄰的血管平滑肌細胞 PDGF-BB和TGFβ1的合成以及細胞增殖、遷移和多種細胞內信號轉導分子激活,。血管內皮細胞釋放的TGFβ1參與了內皮細胞自身增殖和遷移的調控,，對血管平滑肌細胞無明顯作用。此外,，血管平滑肌細胞合成PDGF-BB和TGFβ1可以通過旁分泌作用反饋調節(jié)血管內皮細胞功能,。
國際同行專家認為，該研究是一項卓越 (excellence) 的創(chuàng)新工作,，在切應力調控血管重建這一復雜過程中,，揭示了細胞-細胞間信息交流中PDGF-BB和TGFβ1兩種分子的不同作用，對于闡明動脈粥樣硬化發(fā)病機制具有重要意義,。（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1019219108
PDGF-BB and TGF-β1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress
Ying-Xin Qia, Jun Jianga, Xiao-Hua Jianga, Xiao-Dong Wanga, Su-Ying Jia, Yue Hana, Ding-Kun Longa, Bao-Rong Shena, Zhi-Qiang Yana, Shu Chienb,1, and Zong-Lai Jianga,1
Abstract
Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm2) and normal shear stress (15 dyn/cm2) were compared. By using Ingenuity Pathway Analysis to identify protein–protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-β1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-β1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-β1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-β1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-β1 participates in the feedback control from VSMCs to ECs.
