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Xiaohan Lu

Medical Instructor in the Department of Medicine
Medicine, Nephrology

Selected Publications


TNF- α from the Proximal Nephron Exacerbates Aristolochic Acid Nephropathy.

Journal Article Kidney360 · January 1, 2024 KEY POINTS: Proximal tubular TNF aggravates kidney injury and fibrogenesis in aristolochic acid nephropathy. Tubular TNF disrupts the cell cycle in injured tubular epithelial cells. TNF-mediated toxic renal injury is independent of systemic immune response ... Full text Link to item Cite

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Journal Article Front Mol Biosci · 2024 Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and b ... Full text Link to item Cite

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

Journal Article J Am Soc Nephrol · October 1, 2023 SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney pro ... Full text Link to item Cite

A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.

Journal Article Kidney Int · March 2023 The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages ... Full text Link to item Cite

Actions of Dendritic Cells in the Kidney during Hypertension.

Journal Article Compr Physiol · August 11, 2022 The immune response plays a critical role in the pathogenesis of hypertension, and immune cell populations can promote blood pressure elevation via actions in the kidney. Among these cell lineages, dendritic cells (DCs), the most potent antigen-presenting ... Full text Link to item Cite

The Immune System in Hypertension: a Lost Shaker of Salt 2021 Lewis K. Dahl Memorial Lecture.

Journal Article Hypertension · July 2022 The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappr ... Full text Link to item Cite

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

Journal Article Hypertension · June 2022 BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bon ... Full text Link to item Cite

IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.

Journal Article Am J Physiol Renal Physiol · February 1, 2022 Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in ... Full text Link to item Cite

Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.

Journal Article JCI Insight · August 9, 2021 The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cel ... Full text Link to item Cite

Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction.

Journal Article Kidney360 · May 27, 2021 BACKGROUND: Twist1 is a basic helix-loop-helix domain-containing transcription factor that participates in diverse cellular functions, including epithelial-mesenchymal transition and the cellular immune response. Although Twist1 plays critical roles in the ... Full text Link to item Cite

Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor.

Journal Article Clin Sci (Lond) · March 26, 2021 Until now, renin-angiotensin system (RAS) hyperactivity was largely thought to result from angiotensin II (Ang II)-dependent stimulation of the Ang II type 1 receptor (AT1R). Here we assessed the role of soluble (pro)renin receptor (sPRR), a product of sit ... Full text Link to item Cite

COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats.

Journal Article Am J Physiol Renal Physiol · October 1, 2020 It has been shown that cyclooxygenase (COX)-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (ANG II)-induced hypertension. However, less is known about the involvement of this mechanism in ANG II-independent hyperten ... Full text Link to item Cite

Actions of immune cells in the hypertensive kidney.

Journal Article Curr Opin Nephrol Hypertens · September 2020 PURPOSE OF REVIEW: Inflammatory processes play a critical role in the pathogenesis of hypertension. Innate and adaptive immune responses participate in blood pressure (BP) elevation and end-organ damage. In this review, we discuss recent studies illustrati ... Full text Link to item Cite

C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking.

Journal Article Hypertension · March 2020 Activated T lymphocytes that infiltrate blood pressure control organs make a critical contribution to the pathogenesis of hypertension. Dendritic cells act as potent antigen-presenting cells to stimulate prohypertensive T cells. However, the mechanisms tha ... Full text Link to item Cite

Soluble (pro)renin receptor regulation of ENaC involved in aldosterone signaling in cultured collecting duct cells.

Journal Article Am J Physiol Renal Physiol · March 1, 2020 We have previously shown that activation of (pro)renin receptor (PRR) induces epithelial Na+ channel (ENaC) activity in cultured collecting duct cells. Here, we examined the role of soluble PRR (sPRR), the cleavage product of PRR in ENaC regulation, and fu ... Full text Link to item Cite

The transcription factor Twist1 in the distal nephron but not in macrophages propagates aristolochic acid nephropathy.

Journal Article Kidney Int · January 2020 Tubulointerstitial disease in the kidney culminates in renal fibrosis that portents organ failure. Twist1, a basic helix-loop-helix protein 38 transcription factor, regulates several essential biological functions, but inappropriate Twist1 activity in the ... Full text Link to item Cite

TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis.

Journal Article Am J Physiol Renal Physiol · January 1, 2020 Nephrotoxic serum nephritis (NTN) models immune-mediated human glomerulonephritis and culminates in kidney inflammation and fibrosis, a process regulated by T lymphocytes. TNF-α is a key proinflammatory cytokine that contributes to diverse forms of renal i ... Full text Link to item Cite

Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.

Journal Article Hypertension · January 2020 FLT3L (Fms-like tyrosine kinase 3 ligand) stimulates the development of classical dendritic cells (DCs). Here we tested the hypothesis that classical DCs drive blood pressure elevation by promoting renal fluid retention. FLT3L-deficient (FLT3L-/-) mice tha ... Full text Link to item Cite

A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation.

Journal Article Circ Res · December 6, 2019 RATIONALE: The ubiquitin-editing protein A20 in dendritic cells (DCs) suppresses NF-κB (nuclear factor-κB) signaling and constrains DC-mediated T-cell stimulation, but the role of A20 in modulating the hypertensive response requires elucidation. OBJECTIVE: ... Full text Link to item Cite

Opposing actions of renal tubular- and myeloid-derived porcupine in obstruction-induced kidney fibrosis.

Journal Article Kidney Int · December 2019 Wnt/β-catenin signaling is essential in the pathogenesis of renal fibrosis. We previously reported inhibition of the Wnt O-acyl transferase porcupine, required for Wnt secretion, dramatically attenuates kidney fibrosis in the murine unilateral ureteral obs ... Full text Link to item Cite

TNF- α from the Proximal Nephron Exacerbates Aristolochic Acid Nephropathy.

Journal Article Kidney360 · January 1, 2024 KEY POINTS: Proximal tubular TNF aggravates kidney injury and fibrogenesis in aristolochic acid nephropathy. Tubular TNF disrupts the cell cycle in injured tubular epithelial cells. TNF-mediated toxic renal injury is independent of systemic immune response ... Full text Link to item Cite

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Journal Article Front Mol Biosci · 2024 Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and b ... Full text Link to item Cite

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

Journal Article J Am Soc Nephrol · October 1, 2023 SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney pro ... Full text Link to item Cite

A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.

Journal Article Kidney Int · March 2023 The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages ... Full text Link to item Cite

Actions of Dendritic Cells in the Kidney during Hypertension.

Journal Article Compr Physiol · August 11, 2022 The immune response plays a critical role in the pathogenesis of hypertension, and immune cell populations can promote blood pressure elevation via actions in the kidney. Among these cell lineages, dendritic cells (DCs), the most potent antigen-presenting ... Full text Link to item Cite

The Immune System in Hypertension: a Lost Shaker of Salt 2021 Lewis K. Dahl Memorial Lecture.

Journal Article Hypertension · July 2022 The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappr ... Full text Link to item Cite

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

Journal Article Hypertension · June 2022 BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bon ... Full text Link to item Cite

IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.

Journal Article Am J Physiol Renal Physiol · February 1, 2022 Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in ... Full text Link to item Cite

Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.

Journal Article JCI Insight · August 9, 2021 The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cel ... Full text Link to item Cite

Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction.

Journal Article Kidney360 · May 27, 2021 BACKGROUND: Twist1 is a basic helix-loop-helix domain-containing transcription factor that participates in diverse cellular functions, including epithelial-mesenchymal transition and the cellular immune response. Although Twist1 plays critical roles in the ... Full text Link to item Cite

Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor.

Journal Article Clin Sci (Lond) · March 26, 2021 Until now, renin-angiotensin system (RAS) hyperactivity was largely thought to result from angiotensin II (Ang II)-dependent stimulation of the Ang II type 1 receptor (AT1R). Here we assessed the role of soluble (pro)renin receptor (sPRR), a product of sit ... Full text Link to item Cite

COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats.

Journal Article Am J Physiol Renal Physiol · October 1, 2020 It has been shown that cyclooxygenase (COX)-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (ANG II)-induced hypertension. However, less is known about the involvement of this mechanism in ANG II-independent hyperten ... Full text Link to item Cite

Actions of immune cells in the hypertensive kidney.

Journal Article Curr Opin Nephrol Hypertens · September 2020 PURPOSE OF REVIEW: Inflammatory processes play a critical role in the pathogenesis of hypertension. Innate and adaptive immune responses participate in blood pressure (BP) elevation and end-organ damage. In this review, we discuss recent studies illustrati ... Full text Link to item Cite

C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking.

Journal Article Hypertension · March 2020 Activated T lymphocytes that infiltrate blood pressure control organs make a critical contribution to the pathogenesis of hypertension. Dendritic cells act as potent antigen-presenting cells to stimulate prohypertensive T cells. However, the mechanisms tha ... Full text Link to item Cite

Soluble (pro)renin receptor regulation of ENaC involved in aldosterone signaling in cultured collecting duct cells.

Journal Article Am J Physiol Renal Physiol · March 1, 2020 We have previously shown that activation of (pro)renin receptor (PRR) induces epithelial Na+ channel (ENaC) activity in cultured collecting duct cells. Here, we examined the role of soluble PRR (sPRR), the cleavage product of PRR in ENaC regulation, and fu ... Full text Link to item Cite

The transcription factor Twist1 in the distal nephron but not in macrophages propagates aristolochic acid nephropathy.

Journal Article Kidney Int · January 2020 Tubulointerstitial disease in the kidney culminates in renal fibrosis that portents organ failure. Twist1, a basic helix-loop-helix protein 38 transcription factor, regulates several essential biological functions, but inappropriate Twist1 activity in the ... Full text Link to item Cite

TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis.

Journal Article Am J Physiol Renal Physiol · January 1, 2020 Nephrotoxic serum nephritis (NTN) models immune-mediated human glomerulonephritis and culminates in kidney inflammation and fibrosis, a process regulated by T lymphocytes. TNF-α is a key proinflammatory cytokine that contributes to diverse forms of renal i ... Full text Link to item Cite

Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.

Journal Article Hypertension · January 2020 FLT3L (Fms-like tyrosine kinase 3 ligand) stimulates the development of classical dendritic cells (DCs). Here we tested the hypothesis that classical DCs drive blood pressure elevation by promoting renal fluid retention. FLT3L-deficient (FLT3L-/-) mice tha ... Full text Link to item Cite

A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation.

Journal Article Circ Res · December 6, 2019 RATIONALE: The ubiquitin-editing protein A20 in dendritic cells (DCs) suppresses NF-κB (nuclear factor-κB) signaling and constrains DC-mediated T-cell stimulation, but the role of A20 in modulating the hypertensive response requires elucidation. OBJECTIVE: ... Full text Link to item Cite

Opposing actions of renal tubular- and myeloid-derived porcupine in obstruction-induced kidney fibrosis.

Journal Article Kidney Int · December 2019 Wnt/β-catenin signaling is essential in the pathogenesis of renal fibrosis. We previously reported inhibition of the Wnt O-acyl transferase porcupine, required for Wnt secretion, dramatically attenuates kidney fibrosis in the murine unilateral ureteral obs ... Full text Link to item Cite

KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis.

Journal Article J Am Soc Nephrol · October 2019 BACKGROUND: Polarized macrophage populations can orchestrate both inflammation of the kidney and tissue repair during CKD. Proinflammatory M1 macrophages initiate kidney injury, but mechanisms through which persistent M1-dependent kidney damage culminates ... Full text Link to item Cite

Twist1 in Infiltrating Macrophages Attenuates Kidney Fibrosis via Matrix Metallopeptidase 13-Mediated Matrix Degradation.

Journal Article J Am Soc Nephrol · September 2019 BACKGROUND: Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix via endocytosis, proteolysis, or both. ... Full text Link to item Cite

Interleukin-1 receptor activation aggravates autosomal dominant polycystic kidney disease by modulating regulated necrosis.

Journal Article Am J Physiol Renal Physiol · August 1, 2019 Autosomal dominant polycystic kidney disease (ADPKD) is associated with increased chemokines, cytokines, and growth factors in the diseased kidney. We found that both isoforms of IL-1, IL-1α and IL-1β, were upregulated in ADPKD tissues. Here, we used a uni ... Full text Link to item Cite

Stimulating Type 1 Angiotensin Receptors on T Lymphocytes Attenuates Renal Fibrosis.

Journal Article Am J Pathol · May 2019 Most forms of chronic kidney disease culminate in renal fibrosis that heralds organ failure. In contrast to the protective effects of globally blocking type 1 angiotensin (AT1) receptors throughout the body, activating AT1 receptors directly on immune cell ... Full text Link to item Cite

Site-1 protease-derived soluble (pro)renin receptor targets vasopressin receptor 2 to enhance urine concentrating capability.

Journal Article JCI Insight · April 4, 2019 The antidiuretic hormone vasopressin (AVP), acting through its type 2 receptor (V2R) in the collecting duct (CD), critically controls urine concentrating capability. Here, we report that site-1 protease-derived (S1P-derived) soluble (pro)renin receptor (sP ... Full text Link to item Cite

Inflammation in Salt-Sensitive Hypertension and Renal Damage.

Journal Article Curr Hypertens Rep · October 30, 2018 PURPOSE OF REVIEW: Low-grade inflammation drives elevations in blood pressure (BP) and consequent target organ damage in diverse experimental models of hypertension. Here, we discuss recent advances elucidating immune-mediated mechanisms of BP elevation an ... Full text Link to item Cite

Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury.

Journal Article Am J Physiol Renal Physiol · September 1, 2018 Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Drug-induced/toxic AKI can be caused by a number of therapeutic agents. Cisplatin is an effective chemotherapeutic agent whose administration is limited by significant nephrotoxicity. ... Full text Link to item Cite

NF-κB-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells.

Journal Article Am J Physiol Cell Physiol · December 1, 2017 (Pro)renin receptor (PRR), a component of the renin-angiotensin system, has emerged as a new regulator of collecting duct function. The present study was designed to investigate the role of PRR in high salt-induced apoptosis in cultured mouse inner medulla ... Full text Link to item Cite

The soluble (Pro) renin receptor does not influence lithium-induced diabetes insipidus but does provoke beiging of white adipose tissue in mice.

Journal Article Physiol Rep · November 2017 Earlier we reported that the recombinant soluble (pro) renin receptor sPRR-His upregulates renal aquoporin-2 (AQP2) expression, and attenuates polyuria associated with nephrogenic diabetes insipidus (NDI) induced by vasopressin type 2 receptor (V2R) antago ... Full text Link to item Cite

Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension.

Journal Article Am J Physiol Renal Physiol · February 1, 2017 The (pro)renin receptor (PRR) is abundantly expressed in the collecting duct (CD) and the expression is further induced by angiotensin II (ANG II). The present study was conducted to investigate the role of CD PRR during ANG II-induced hypertension and to ... Full text Link to item Cite

Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity.

Journal Article Hypertension · February 2017 A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, hi ... Full text Link to item Cite

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4.

Journal Article J Am Soc Nephrol · October 2016 Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4 Notably, EP4 also controls urinary concentration through regulation of ... Full text Link to item Cite

Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy.

Journal Article Physiol Genomics · October 1, 2016 We investigated the expression and function of serum response factor (SRF) in endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells (GEnCs) of diabetic nephropathy (DN). The expression of SRF, endothelial markers (VE-cadherin, CD31), a ... Full text Link to item Cite

Activation of ENaC in collecting duct cells by prorenin and its receptor PRR: involvement of Nox4-derived hydrogen peroxide.

Journal Article Am J Physiol Renal Physiol · June 1, 2016 The collecting duct (CD) has been recognized as an important source of prorenin/renin, and it also expresses (pro)renin receptor (PRR). The goal of this study was to examine the hypothesis that prorenin or renin via PRR regulates epithelial Na(+) channel ( ... Full text Link to item Cite

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor.

Journal Article Proc Natl Acad Sci U S A · March 29, 2016 The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the anti ... Full text Link to item Cite

Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system.

Journal Article BMC Med · November 10, 2015 BACKGROUND: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The ... Full text Link to item Cite

Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla.

Journal Article Hypertension · August 2014 Angiotensin II (Ang II) stimulates (pro)renin receptor (PRR) expression in the renal collecting duct, triggering the local renin response in the distal nephron. Our recent study provided evidence for involvement of cyclooxygenase-2-prostaglandin E2 pathway ... Full text Link to item Cite

COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla.

Journal Article Am J Physiol Renal Physiol · July 1, 2014 (Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. Th ... Full text Link to item Cite