Mannose-binding lectin-associated serine protease-1 cleaves plasminogen and plasma fibronectin: prefers plasminogen over known fibrinogen substrate

Choudhary, Komal; Patel, Pankaj Kumar; Are, V.; Makde, Ravindra D.; Hajela, Krishnan

doi:10.1097/mbc.0000000000001074

Cited by 5 publications

(7 citation statements)

References 31 publications

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“…S8B ). Interestingly, some of these proteins have been related to immune functions, e.g., SERPINA 3 [ 24 ], MASP1 [ 25 ] and AI182371 (GO annotation), or to pathophysiological conditions of the CNS, e.g., SERPINA 3 [ 26 ] and PZP [ 27 , 28 ]. The levels of the other 11 proteins were also modified after β-RA and VA treatment compared to vehicle treatment, although they were not altered in Coq9 R239X mice compared to wild-type mice ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

et al. 2022

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Section: Resultsmentioning

confidence: 99%

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

et al. 2022

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“…[21] Fibronectin Thrombosis regulation and haemostasis maintenance. [35,40] Kininogen-1 Help in positioning of prekallikrein and factor XI next to factor XII during intrinsic pathway of blood coagulation; inhibits thrombin-and plasmin-induced thrombocytes aggregation. [41,42] PAR-4 Maintenance of hemostasis by platelets activation during coagulation cascade.…”

Section: Austin Publishing Groupmentioning

confidence: 99%

“…The plasmin/ A2AP complex levels are increased in acute stroke, myocardial infarction, and arterial fibrillation [34]. rMASP-1 dissolves clots by activating fibrin-associated plasminogen [35]. Thrombin activates FXIII which helps in forming crosslinks between fibrin monomers, and eventually an insoluble fibrin clot.…”

Section: Austin Publishing Groupmentioning

confidence: 99%

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Fibrinogen Cleavage by Lectin Pathway Proteases: Roles and Implications

et al. 2023

jblooddisordl

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The lectin pathway proteases (MASPs) are diverse in regard to their substrate selectivity and also have substrates outside the complement pathway. These proteases have been reported to cleave proteins of the coagulation cascade. MASP-1 has thrombin-like activity and therefore cleaves fibrinogen, fibrin and prothrombin. MASP-2 also participates in coagulation by cleaving prothrombin. Thus, these proteases are key players in the process of thrombosis and thrombolysis, therefore have implications in thrombotic vascular diseases. The cleaved fragments of fibrinogen and fibrin, consequently produced during coagulation and fibrinolysis, are important in the repair process and hence may have involvement in inflammatory and fibro-proliferative diseases. Also, altered levels of MBL and its associated serine proteases reported to be involved in different diseases such as cardiovascular diseases, diabetes, cancer, sepsis, stroke, COVID-19 etc. may have a role in thrombosis and thrombolysis. Upregulated lectin pathway-associated proteins predispose towards autoimmune disease susceptibility and may also exhibit off-target activities resulting in clot formation. Thus, the lectin pathway and its associated proteases are of great importance in normal circumstances where it plays a role in the maintenance of hemostasis and homeostasis, playing a preventive role in infections. Modulation in the level of MASPs proteases could be developed as a promising approach to treat a variety of infections and diseases.

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“…However, plasma kallikrein has been recognized as a pro-convertase, with anaphylatoxin production ( 6 ). In addition to anaphylatoxin generation, complement proteases promote plasminogen activation ( 7 ), with plasmin production that in turn triggers KKS. This latter proteolytic system directly cleaves circulating high molecular weight kininogen, subsequently generating BK production.…”

Section: Introductionmentioning

confidence: 99%

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE

Drouet

López‐Lera

Ghannam³

et al. 2022

Front. Allergy

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Hereditary angioedema with C1 Inhibitor deficiency (C1-INH-HAE) is caused by a constellation of variants of the SERPING1 gene (n = 809; 1,494 pedigrees), accounting for 86.8% of HAE families, showing a pronounced mutagenic liability of SERPING1 and pertaining to 5.6% de novo variants. C1-INH is the major control serpin of the kallikrein–kinin system (KKS). In addition, C1-INH controls complement C1 and plasminogen activation, both systems contributing to inflammation. Recognizing the failed control of C1s protease or KKS provides the diagnosis of C1-INH-HAE. SERPING1 variants usually behave in an autosomal-dominant character with an incomplete penetrance and a low prevalence. A great majority of variants (809/893; 90.5%) that were introduced into online database have been considered as pathogenic/likely pathogenic. Haploinsufficiency is a common feature in C1-INH-HAE where a dominant-negative variant product impacts the wild-type allele and renders it inactive. Small (36.2%) and large (8.3%) deletions/duplications are common, with exon 4 as the most affected one. Point substitutions with missense variants (32.2%) are of interest for the serpin structure–function relationship. Canonical splice sites can be affected by variants within introns and exons also (14.3%). For noncanonical sequences, exon skipping has been confirmed by splicing analyses of patients' blood-derived RNAs (n = 25). Exonic variants (n = 6) can affect exon splicing. Rare deep-intron variants (n = 6), putatively acting as pseudo-exon activating mutations, have been characterized as pathogenic. Some variants have been characterized as benign/likely benign/of uncertain significance (n = 74). This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. Rare benign variants could contribute as disease modifiers. Gonadal mosaicism in C1-INH-HAE is rare and must be distinguished from a de novo variant. Situations with paternal or maternal disomy have been recorded (n = 3). Genotypes must be interpreted with biological investigation fitting with C1-INH expression and typing. Any SERPING1 variant reminiscent of the dysfunctional phenotype of serpin with multimerization or latency should be identified as serpinopathy.

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Mannose-binding lectin-associated serine protease-1 cleaves plasminogen and plasma fibronectin: prefers plasminogen over known fibrinogen substrate

Cited by 5 publications

References 31 publications

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

Fibrinogen Cleavage by Lectin Pathway Proteases: Roles and Implications

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE

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