Tissue Matrix Deposition Research Articles

Ginsenosides: potential therapeutic source for fibrosis-associated human diseases

Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epithelial–mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

Serum concentrations of IL-17A, IL-17B, IL-17E and IL-17F in patients with systemic sclerosis.

IntroductionImmune system activation, microvascular abnormalities and extracellular matrix deposition in tissues play roles in systemic sclerosis (SSc). Th17 cells producing interleukin (IL)-17 are involved in the pathogenesis of many autoimmune-mediated inflammatory diseases; however, the role of IL-17 in SSc remains unclear.Material and methodsThe concentrations of IL-17A, IL-17B, IL-17E, and IL-17F in the serum of patients with SSc and in the healthy control group were assessed with regard to type of the disease – whether limited (lSSc) or diffuse (dSSc) – and symptoms.ResultsNo difference was found between patients with SSc and the control group as regards the serum concentration of IL-17A. However, IL-17B and IL-17E levels in patients with SSc, and its types diffuse and limited were higher (p < 0.001) compared to the control. The serum level of IL-17F was higher in SSc (p < 0.005) and lSSc (p < 0.05) compared to the control. Serum concentration of IL-17B was elevated in SSc patients with renal abnormalities (p < 0.05) compared to those without. Serum levels of IL-17B correlated with the levels of IL-17E in patients with SSc (r = 0.54, p < 0.05).ConclusionsIncreased synthesis of IL-17B, IL-17E and IL-17F appears to play a role in the pathogenesis of SSc, in contrast to IL-17A. Higher levels of IL-17B and IL-17E are associated with the development of both lSSc and dSSc, whereas IL-17F is associated with lSSc only. Further studies are needed to elucidate their role in the pathogenesis of the disease.

Matrix metalloproteinases in early human liver development.

Matrix metalloproteinases (MMPs) regulate matrix deposition in tissues. Collagens I, III, and IV are involved in early human liver development. To establish whether MMPs specific for these collagens participate in early human liver development, we localized immunohistochemically MMP-1 and MMP-13 (for collagens I and III) and MMP-2 and MMP-7 (for collagen IV) in the early human liver anlage [6th-10th gestational week (GW)]. MMP-1 was found from the 6th GW onward in hepatocytes and later also in outer limiting plate hepatocytes, early bile ducts, and periportal mesenchymal cells. In the 6th GW, MMP-2 was found only in microvascular endothelium. In the 7th GW, MMP-2 was also detected in hepatocytes. From the 9th GW onward, MMP-2 was detectable in all hepatocytes and erythropoietic, endothelial, and periportal mesenchymal cells. MMP-7 was present in the 6th GW in some hepatocytes and endothelial cells, but from the 7th GW onward, only in hematopoietic cells. MMP-13 was found exclusively in hematopoietic cells. This study has shown that production of MMP -1, MMP-2, MMP-7, and MMP-13 during human liver development already occurs from the 6th GW. At this time-point their substrates are only traces or are not yet present in the tissue. A possible role of MMPs in early liver development is discussed.

Can wound healing be a paradigm for tissue repair?

This paper is written in the hope, if not the conviction, that it will be helpful to investigators of muscle physiology and development. Its thesis is that cell growth, connective tissue matrix deposition, and angiogenesis are stimulated in wounds in response to NAD+ depletion caused by a burst in lactate generation. We surmise that muscle development may also involve this metabolic control.