Extracellular matrix degradation in liver fibrosis: Biochemistry ..

ECM assembly is controlled by its rate of synthesis and degradation, ..

Extracellular matrix - Wikipedia

In hypertensive patients with LVH, there are increased levels of circulating TIMP1 but diminished levels of circulating MMP1 and collagen type I telopeptide (CITP, a breakdown product of collagen) (), compared with hypertensive patients without LVH. More recently, Ahmed et al. showed that patients with hypertension but normal LV structure and function had normal plasma MMP and TIMP levels (). By contrast, patients with hypertension and LVH had decreased levels of MMP2 and MMP13 and increased levels of MMP9. Only patients with LVH and heart failure had increased levels of TIMP1. Based on these data, they concluded that decreased ECM degradation was associated with LVH and diastolic dysfunction. These studies highlight a potential beneficial effect of specific MMP9 inhibitors in HHD and raise the general concept that altering the balance of degradation and synthesis of ECM might have clinical utility.

hypertrophy, and apoptosis as well as synthesis and degradation of the ECM [20, 21].

In biology, the extracellular matrix (ECM) ..

Abstract: This paper reviews biodegradable synthetic polymers focusing on their potential in tissue engineering applications. The major classes of polymers are briefly discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are indicated based on studies reported in the literature. A vast majority of biodegradable polymers studied belongs to the polyester family, which includes polyglycolides and polylactides. Some disadvantages of these polymers in tissue engineering applications are their poor biocompatibility, release of acidic degradation products, poor processability and loss of mechanical properties very early during degradation. Other degradable polymers such as polyorthoesters, polyanhydrides, polyphosphazenes, and polyurethanes are also discussed and their advantages and disadvantages summarised. With advancements in tissue engineering it has become necessary to develop polymers that meet more demanding requirements. Recent work has focused on developing injectable polymer compositions based on poly (propylene fumarate) and poly (anhydrides) to meet these requirements in orthopaedic tissue engineering. Polyurethanes have received recent attention for development of degradable polymers because of their great potential in tailoring polymer structure to achieve mechanical properties and biodegradability to suit a variety of applications.

Nodular expansion of glomerular mesangiumwith increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50-60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulsechase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S ([35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in ∼40-50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged. Thus the increase in matrix transcripts and synthesis of FN, LM, and T-IV contributes significantly to the increased accumulation of these matrix proteins in mesangial cells grown in 30 mM glucose and, similarly, may also be involved in the increased deposition of these proteins in the diabetic mesangium.


The role of microRNAs in skin fibrosis | SpringerLink

N2 - Nodular expansion of glomerular mesangiumwith increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50-60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulsechase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S ([35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in ∼40-50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged. Thus the increase in matrix transcripts and synthesis of FN, LM, and T-IV contributes significantly to the increased accumulation of these matrix proteins in mesangial cells grown in 30 mM glucose and, similarly, may also be involved in the increased deposition of these proteins in the diabetic mesangium.