Collagen synthesis and degradation in polyneuropathy and myopathies

Abstract

To determine the mechanisms underlying the changes in collagen metabolism responsible for muscle fibrosis in patients with neuromuscular diseases, the synthesis and degradation of collagens was studied in muscles of patients with polyneuropathy and noninflammatory myopathies. The mRNA levels for type I, III, and IV collagens and immunohistochemical staining intensities for collagen propeptides and telopeptides were increased in polyneuropathy, suggesting enhanced synthesis of collagens. In myopathy, the mRNA levels were at the control level. Matrix metalloproteinase (MMP)-2 mRNA level was increased in polyneuropathy, although the quantity of proMMP-2 was not changed. An increase in type IV collagen concentration and proMMP-9 expression was observed in polyneuropathy but not in myopathies. Our results suggest that intramuscular accumulation of type IV collagen occurs in polyneuropathy, possibly leading to thickening of the capillary and muscle fiber basement membranes. This may complicate the transportation of nutrients and cellular excreta between blood and muscle cells.

Effects of 660 and 780 nm low‐level laser therapy on neuromuscular recovery after crush injury in rat sciatic nerve

“…These changes require the action of proteolytic zinc‐containing enzymes called matrix metalloproteinases (MMPs), which play a critical role in the ECM reorganization. MMPs are secreted by Schwann cells, intramuscular axons, muscle satellite cells, and fibroblasts into the skeletal muscle at the neuromuscular junction (NMJ) and around muscle fibers 11,14–16.…”

“…Nevertheless, only a few studies have investigated MMPs in neuromuscular diseases 11,12,14,17–19. Studies on nerve crush injury suggest that MMP‐2 and MMP‐9 are involved in facilitating axonal growth along the peripheral nerve via basal lamina remodeling 12,13.…”

Electrical stimulation of cardiomyocytes activates mitochondrial matrix metalloproteinase causing electrical remodeling

“…Considering the large family of MMPs, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are the key ones involved in the ECM remodeling of heart with both changing demands and response to injury (24). Both are known to break down non–fibrillar-forming type IV collagen and denatured interstitial collagens (1). …”

Electrical stimulation increases matrix metalloproteinase‐2 gene expression but does not change its activity in denervated rat muscle

“…Profound loss of mass and force‐generating ability occur after denervation 3, 4, 9, 13, 16. Changing demand in diseased muscle tissue, such as after denervation, causes remodeling of the muscle extracellular matrix (ECM),8 and matrix metalloproteinases (MMPs) have a critical role in ECM modification 1, 8, 28. MMPs are a family of zinc‐dependent proteolytic enzymes composed of up to 22 members encompassing collagenase, gelatinase, stromelysin, and membrane‐type MMP subfamilies 5, 28.…”