[Mechanotransduction and cellular response--a challenge toward development of mechano-pharmacology].
Mechanoreception and subsequent cellular/molecular mechanisms of signal transduction pathways in response to mechanical stresses, including hemodynamic factors, passive stretching, and exercise, are ubiquitous in living organisms. Of these, the cardiovascular system involving the heart and blood vessels is known to be particularly sensitive to mechanical stimuli, for example, stretching and intraluminal pressurization, which might mimic an acute and/or chronic change in blood pressure and flow, induce a variety of responses including contraction, activation of various kinases and ionic channels, production of vasoactive substances, gene expression, and phenotype changes. We have started to clarify the mechanisms underlying this basic principle in the cardiovascular system as it is now generally considered that obesity and a lack of exercise are serious risk factors for cardiovascular diseases such as hypertension, atherosclerosis, and type 2 diabetes. We further extended our research field of mechanotransduction into adipocytes, skeletal muscle cells, and pancreatic beta cells, all of which are related to the core concerns in cardiovascular disease, including the so-called metabolic syndrome. In the present article, we discuss briefly the prologue to our study of mechanotransduction and several topics in the recent progress in this interesting area. We also emphasize that it is important to recognize biomechanical factors and control them not only for improvement in our knowledge of health and disease but also for the development of new drugs.
Nakayama
Koichi
K
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Japan. nakyamk@ys7.u-shizuoka-ken.ac.jp
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001696:Biomechanical Phenomena; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology*; D002320:Cardiovascular Physiological Phenomena; D002454:Cell Differentiation; D015195:Drug Design; D015444:Exercise; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009765:Obesity; D010741:Phospholipases A / Q000378:metabolism; D012307:Risk Factors; D013314:Stress, Mechanical
D010741:Phospholipases A; D005947:Glucose