Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract
IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glom...
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2024-03-01
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| author | Jingyi Li Jingyi Li Jingyi Li Jingyi Li Jingyi Li Yaping Dong Yaping Dong Yaping Dong Yaping Dong Yaping Dong Feifei Chen Feifei Chen Feifei Chen Feifei Chen Feifei Chen Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Pei Chen Pei Chen Pei Chen Pei Chen Pei Chen Hongyu Li Hongyu Li Hongyu Li Hongyu Li Hongyu Li Sufang Shi Sufang Shi Sufang Shi Sufang Shi Sufang Shi Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Li Zhu Li Zhu Li Zhu Li Zhu Li Zhu Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Lijun Liu Lijun Liu Lijun Liu Lijun Liu Lijun Liu Xinfang Xie Feng Yu Jing Jin Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang Hong Zhang Hong Zhang |
| author_facet | Jingyi Li Jingyi Li Jingyi Li Jingyi Li Jingyi Li Yaping Dong Yaping Dong Yaping Dong Yaping Dong Yaping Dong Feifei Chen Feifei Chen Feifei Chen Feifei Chen Feifei Chen Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Pei Chen Pei Chen Pei Chen Pei Chen Pei Chen Hongyu Li Hongyu Li Hongyu Li Hongyu Li Hongyu Li Sufang Shi Sufang Shi Sufang Shi Sufang Shi Sufang Shi Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Li Zhu Li Zhu Li Zhu Li Zhu Li Zhu Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Lijun Liu Lijun Liu Lijun Liu Lijun Liu Lijun Liu Xinfang Xie Feng Yu Jing Jin Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang Hong Zhang Hong Zhang |
| author_sort | Jingyi Li |
| collection | DOAJ |
| description | IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors. |
| first_indexed | 2024-04-24T23:49:02Z |
| format | Article |
| id | doaj.art-bd48204f44c647858dee1285c396492a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T23:49:02Z |
| publishDate | 2024-03-01 |
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| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bd48204f44c647858dee1285c396492a2024-03-15T04:26:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13683221368322Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extractJingyi Li0Jingyi Li1Jingyi Li2Jingyi Li3Jingyi Li4Yaping Dong5Yaping Dong6Yaping Dong7Yaping Dong8Yaping Dong9Feifei Chen10Feifei Chen11Feifei Chen12Feifei Chen13Feifei Chen14Hongyu Yang15Hongyu Yang16Hongyu Yang17Hongyu Yang18Hongyu Yang19Pei Chen20Pei Chen21Pei Chen22Pei Chen23Pei Chen24Hongyu Li25Hongyu Li26Hongyu Li27Hongyu Li28Hongyu Li29Sufang Shi30Sufang Shi31Sufang Shi32Sufang Shi33Sufang Shi34Xujie Zhou35Xujie Zhou36Xujie Zhou37Xujie Zhou38Xujie Zhou39Li Zhu40Li Zhu41Li Zhu42Li Zhu43Li Zhu44Yuemiao Zhang45Yuemiao Zhang46Yuemiao Zhang47Yuemiao Zhang48Yuemiao Zhang49Lijun Liu50Lijun Liu51Lijun Liu52Lijun Liu53Lijun Liu54Xinfang Xie55Feng Yu56Jing Jin57Jicheng Lv58Jicheng Lv59Jicheng Lv60Jicheng Lv61Jicheng Lv62Hong Zhang63Hong Zhang64Hong Zhang65Hong Zhang66Hong Zhang67Renal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaDepartment of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, ChinaDepartment of Nephrology, Peking University International Hospital, Beijing, ChinaNorthwestern University Feinberg School of Medicine, Division of Nephrology, Chicago, IL, United StatesRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaState Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, ChinaIntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1368322/fullIgA nephropathycomplement factor Hmouse modelthe alternative complement pathwayproteinuria |
| spellingShingle | Jingyi Li Jingyi Li Jingyi Li Jingyi Li Jingyi Li Yaping Dong Yaping Dong Yaping Dong Yaping Dong Yaping Dong Feifei Chen Feifei Chen Feifei Chen Feifei Chen Feifei Chen Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Hongyu Yang Pei Chen Pei Chen Pei Chen Pei Chen Pei Chen Hongyu Li Hongyu Li Hongyu Li Hongyu Li Hongyu Li Sufang Shi Sufang Shi Sufang Shi Sufang Shi Sufang Shi Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Xujie Zhou Li Zhu Li Zhu Li Zhu Li Zhu Li Zhu Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Yuemiao Zhang Lijun Liu Lijun Liu Lijun Liu Lijun Liu Lijun Liu Xinfang Xie Feng Yu Jing Jin Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang Hong Zhang Hong Zhang Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract Frontiers in Immunology IgA nephropathy complement factor H mouse model the alternative complement pathway proteinuria |
| title | Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract |
| title_full | Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract |
| title_fullStr | Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract |
| title_full_unstemmed | Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract |
| title_short | Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract |
| title_sort | heterozygous mutations in factor h aggravate pathological damage in a stable iga deposition model induced by lactobacillus casei cell wall extract |
| topic | IgA nephropathy complement factor H mouse model the alternative complement pathway proteinuria |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1368322/full |
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