Title : The role of growth factors on extracellular matrix and morphogenesis: The Chinese concept of phlegm (TCM) revisited
We suggest a role for growth factors in a staged process of Phlegm, an ancient concept in traditional East Asian medicine. Chronic stagnation of interstitial fluids constitutes a pre-phlegm stage. Venous overfilling in heart failure and/or the renin-angiotensin-aldosterone system may play a constitutive role. Central venous- and hydrostatic pressure burdens not only cava vessels but also azygos veins, perivertebral veins (Botson) and portal system as hydrostatically communicating vessels. Protophlegm stage appears when interstitial pressure is no longer intercepted by lymphatic drainage. Growth factors play a role in endothelialization of lymphatic tissue, hindering active transport by the lymphangions. Phlegm stage II is characterized by the role of growth factors in fibrogenesis with the transformation of fibroblasts into myofibroblasts. Macrophages type 2 predominate this fibrogenesis. Growth factors play a role in the morphogenesis of benign- and malign neoformation in phlegm stage III. Macrophage type 2 may induce neo-angiogenesis into an anoxemic region, becoming tumor-associated. Epigenetic influences may express transforming growth factor into unshielded tumor growth. Phlegm stage IV is characterized by the role of thermogenetic brown adipose tissue in erythropoietic proximal red bone marrow, promoting metastasis of breast- and prostate cancer in bone. microRNA’s could play a role as diagnostic and prognostic biomarkers for cancer.