Chronic kidney disease is detected in 8–15% of the world’s population. Along with fibrotic changes, it can lead to a complete loss of organ function. Therefore, a better understanding of the onset of the pathological process is required. To address this issue, we examined the interaction between mast cells (MCs) and cells in fibrous and intact regions, focusing on the role of MC proteases such as tryptase, chymase, and carboxypeptidase A3 (CPA3). MCs appear to be involved in the development of inflammatory and fibrotic changes through the targeted secretion of tryptase, chymase, and CPA3 to the vascular endothelium, nephron epithelium, interstitial cells, and components of intercellular substances. Protease-based phenotyping of renal MCs showed that tryptase-positive MCs were the most common phenotype at all anatomic sites. The infiltration of MC in different anatomic sites of the kidney with an associated release of protease content was accompanied by a loss of contact between the epithelium and the basement membrane, indicating the active participation of MCs in the formation and development of fibrogenic niches in the kidney. These findings may contribute to the development of novel strategies for the treatment of tubulointerstitial fibrosis.

A number of sarcolemma proteins are responsible for muscle fiber repair. Dysferlin encoded by the DYSF gene is one of these proteins. Dysferlin promotes membrane repair in striated muscle fibers (MFs). Mutations in DYSF lead to loss of or decreased dysferlin expression, impaired membrane repair in MF, and its destruction, clinically manifesting as dysferlinopathy. Preclinical studies of cell and gene therapies aimed at restoring impaired muscle regeneration require well-characterized small animal models. Our investigation aimed to distinguish the histopathological features of a mouse strain lacking dysferlin expression (Bla/J strain). Ultrastructural changes in the sarcolemma, mitochondria and contractile apparatus were observed. It was shown that postnatal histogenesis of skeletal muscles in genetically determined dysferlin deficiency is characterized by a higher proportion of necrotic muscle fibers, compensatory hypertrophy of muscle fibers with their subsequent atrophy, and decreases in proliferative activity and the level of myogenic differentiation of myogenic progenitor cells compared to wild-type mice (C57Bl/6).

BACKGROUND: With the sharp increase in mine-explosive injuries, one of the key tasks of modern histology is to assess the morphogenesis of high-energy limb tissue damage. AIM: This study aimed to characterize striated skeletal muscle tissue in the zone of mine-explosive limb segment avulsion during the early post-traumatic period (days 1–4). METHODS: Histological methods (hematoxylin and eosin staining and Martius Scarlet Blue [MSB] staining for fibrin age determination), immunohistochemical and immunofluorescence techniques (antibodies to CD3, CD20, CD31 [Platelet Endothelial Cell Adhesion Molecule-1], CD68, and NETs [Neutrophil Extracellular Traps]), transmission electron microscopy, and morphometric analyses were applied. RESULTS: Post-traumatic pathological changes affected both muscle tissue (necrosis, fiber fragmentation, traumatic edema) and endomysial and perimysial connective tissue (traumatic edema, fibrin infiltration). Disruption of the cytoskeletal structure (sarcomeres), loss of myosatellite cells, and endothelial cell death in capillaries were observed. Local hemodynamic disturbances manifested as mosaic thrombosis, embolism, and hemorrhage. Within the first 24 hours, arterial and arteriolar spasms led to reduced tissue perfusion. Partial resolution of the spasms by day 4 likely corresponded to the second stage of traumatic shock (the torpid phase). Among leukocytes, CD68+ macrophages were the first to respond, with extravasation beginning on day 2 after injury. A similar trend was observed for CD3+ T cells. CD20+ B cells showed no morphological signs of reactivity during this period. NET formation was observed both intravascularly and in the extravascular compartment. CONCLUSION: Structural and ultrastructural changes in skeletal muscle tissue within the first 4 days after mine-explosive injury have been characterized.

Infertility is an important personal and society disease, of which the male factor represents half of all causes. One of the aspects less studied in male infertility is the immunological testicular microenvironment. Mast cells (MCs), having high potential for regulating spermatogenesis due to fine-tuning the state of the integrative buffer metabolic environment, are one of the most crucial cellular subpopulations of the testicular interstitium. One important component of the MC secretome is proteases that can act as proinflammatory agents and in extracellular matrix (ECM) remodeling. In the testis, MCs are an important cell component of the testicular interstitial tissue (TIT). However, there are still no studies addressing the analysis of a specific MC protease—carboxypeptidase A3 (CPA3)—in cases with altered spermatogenesis. The cytological and histotopographic features of testicular CPA3+ MCs were examined in a study involving 34 men with azoospermia. As revealed, in cases with non-obstructive azoospermia, a higher content of CPA3+ MCs in the TIT and migration to the microvasculature and peritubular tissue of seminiferous tubules were observed when compared with cases with obstructive azoospermia. Additionally, a high frequency of CPA3+ MCs colocalization with fibroblasts, Leydig cells, and elastic fibers was detected in cases with NOA. Thus, CPA3 seems to be of crucial pathogenetic significance in the formation of a profibrogenic background of the tissue microenvironment, which may have direct and indirect effects on spermatogenesis.